Sei sulla pagina 1di 48

Brain Research Bulletin 73 (2007) 155202

Review

Muscle proprioceptive feedback and spinal networks


U. Windhorst
Center for Physiology and Pathophysiology, University of Goettingen, Humboldtallee 23, D-37073 Goettingen, Germany Received 15 March 2007; accepted 15 March 2007 Available online 17 April 2007

Abstract This review revolves primarily around segmental feedback systems established by muscle spindle and Golgi tendon organ afferents, as well as spinal recurrent inhibition via Renshaw cells. These networks are considered as to their potential contributions to the following functions: (i) generation of anti-gravity thrust during quiet upright stance and the stance phase of locomotion; (ii) timing of locomotor phases; (iii) linearization and correction for muscle nonlinearities; (iv) compensation for muscle lever-arm variations; (v) stabilization of inherently unstable systems; (vi) compensation for muscle fatigue; (vii) synergy formation; (viii) selection of appropriate responses to perturbations; (ix) correction for intersegmental interaction forces; (x) sensory-motor transformations; (xi) plasticity and motor learning. The scope will at times extend beyond the narrow connes of spinal circuits in order to integrate them into wider contexts and concepts. 2007 Elsevier Inc. All rights reserved.
Keywords: Spinal cord; Motoneurons; Muscle spindles; Golgi tendon organs; Recurrent inhibition

Contents
1. 2. 3. 4. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Organization of scratch reexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Rhythmogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Generation of upright body posture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Generation of anti-gravity thrust and stiffness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.1. Decerebrate rigidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1.2. Core stretch reex circuit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Reciprocal Ia inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.1. Prevalence of recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.2. Core recurrent inhibitory circuits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Muscle proprioceptive feedback and recurrent inhibition in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Muscle spindles and Golgi tendon organs in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.1. Golgi tendon organ discharge in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.2. Muscle spindle discharge in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.3. Follow-up length servo hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.4. Servo-assistance hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.5. - and -motoneuron discharge patterns in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1.6. Supraspinal and sensory inputs to - and -motoneurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Modulation of segmental sensory input by presynaptic inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. Reciprocal inhibition in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 157 159 159 160 160 160 162 162 163 163 164 164 164 164 164 164 164 166 166 167

5.

Tel.: +49 551 380405; fax: +49 551 3792135. E-mail address: siggi.uwe@t-online.de.

0361-9230/$ see front matter 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.brainresbull.2007.03.010

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Recurrent inhibition in action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4.1. Recurrent inhibition in cat ctive locomotion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4.2. Recurrent inhibition of reciprocal inhibition in cat ctive locomotion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5. Compensation for muscle properties and joint nonlinearities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.1. Linearization of muscle stiffness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.2. Coping with muscle forcelengthvelocity relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.3. Compensation for joint lever-arm variations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5.4. In search of a role for Golgi tendon organs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6. Spinal actions of group Ib afferents from Golgi tendon organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7. Sensory force feedback during the stance phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7.1. Contributions of sensory receptors to force feedback . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7.2. Golgi tendon organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7.3. Muscle spindle group Ia afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7.4. Muscle spindle group II afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7.5. Intermediate summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.8. Interactions between sensory feedback and pattern generators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.8.1. Stance-to-swing transition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.8.2. Drawing inferences and making choices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. Stabilization of motor output . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1. Positive force feedback: risk of instability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2. Motor output uctuations, muscle proprioceptors and recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2.1. Physiological tremor and muscle proprioceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2.2. Physiological tremor and recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2.3. Intermittent motor control and muscle proprioceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3. Compensation for reex delays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.1. Compensation of muscle-unit dynamics by -motoneuron discharge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.2. Phase advance by muscle spindle dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3.3. Phase advance by recurrent inhibition? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7. Compensation for muscle fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1. Actions of the stretch reex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2. Muscular wisdom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1. -Motoneuron discharge adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.2. Diminishing descending motor commands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.3. Diminishing support from neuromodulatory systems? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.4. Diminishing facilitation from muscle spindle afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.5. Actions of chemosensitive group IIIIV muscle afferents on spinal neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.6. Actions of chemosensitive group IIIIV muscle afferents on -motoneurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.7. Actions of chemosensitive group IIIIV muscle afferent bers on -motoneurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.8. Actions on Ib inhibitory interneurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.9. Actions on recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.10. Actions on interneurons mediating presynaptic inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8. Summary and comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9. Global roles of proprioceptive afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1. The redundancy problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2. Global variables of limb geometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1. Cat quiet stance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2. Cat and human locomotion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.3. Biomechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.4. Neural control mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3. Synergies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4. Involvement of muscle proprioceptors and recurrent inhibition in synergy formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.1. Coping with muscle complexity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.2. Coping with multiple degrees of freedom at a joint . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.3. Intermediate summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.4. Heteronymous connections of muscle spindle group Ia afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.5. Heterogenic connections of muscle spindle group II afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.6. Heterogenic connections of Golgi tendon organ afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.7. Heterogenic connections of recurrent inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4.8. Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10. Postural maintenance and adjustments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1. Multiplicity of body schemata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2. Postural body schema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5.4.

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14.

Role of proprioceptors in human body sway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.1. The case against group Ia afferents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3.2. Alternative sensory afferents involved in sway control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4. Role of proprioceptors in human postural reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5. Automatic postural responses in cats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6. Anticipatory postural adjustments to self-generated movements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Proprioceptive feedback in intersegmental interaction dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.1. Cat paw shake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2. Cat walking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3. Human arm reaching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.4. Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Plasticity, adaptability and learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1. Learning kinematics and dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.2. Restoration of function after spinal cord injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.3. Plasticity of the stance support system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4. A hypothesis on the role of recurrent inhibition in learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4.1. Back-propagating action potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4.2. Inuence of inhibition on back-propagating action potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4.3. Corollaries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4.4. Operation of the model after neurectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Transformations revisited . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1. Spatial representations and transformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.2. Coding of kinematics and kinetics in dorsal spinocerebellar tract cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3. Kinematickinetic mixtures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Final comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10.3.

184 184 185 185 185 186 186 186 187 187 187 187 187 188 188 189 189 189 190 190 190 190 191 191 193 193 193 193

1. Introduction Can sense be made of spinal interneuron circuits? [247]. Already two decades ago, Loeb [214] wrote: Those whose experiments have forced us to confront the embarassment of riches in the workings of the spinal cord must ask whether it is useful to continue to collect yet more inexplicable data. Those who believed the spinal cord and peripheral motor plant to be well-understood and thus turned their attentions to higher centers of motor planning and coordination (e.g. cerebral cortex and cerebellum) now nd that their edices are built upon the shifting sands of spinal segmental circuitry (Stuart, D.G., unpublished) (p. 111). Addressing the sense of the spinal Renshaw cell (intercalated in the inhibitory circuit from motor axon collaterals to ventral horn neurons and named in honor of its discoverer: Renshaw [308]), Zev Rymer felt that, given the simplicity of the circuit, and its direct proximity to motor outow, our failure to clarify the function of the Renshaw neuron is an embarassment, and does not generate condence that computational approaches used to describe complex neural circuits will yield useful answers (cited in ref. [391], p. 520). Does our quest for understanding spinal circuits end in embarassment? Yes and no, as discussed below. As requested by the editor, this review will revolve primarily around segmental feedback systems established by muscle spindle and Golgi tendon organ afferents (muscle proprioceptive1
1 The term proprioception is ambivalent because it is composed of the Latin word proprius (own) and a truncated second part, which could refer to recep-

afferents), as well as spinal recurrent inhibition via Renshaw cells. At rst glimpse, this association appears somewhat arbitrary, but it has a long tradition. The discussion will thus focus on spinal circuits, but since segments neither in the spinal cord nor in the body and limbs are isolated, the view will at times have to y out beyond the narrow connes of spinal circuits in order to integrate them into wider concepts. The literature on these issues is immense, and the selection is necessarily restrictive and subjective. 2. Organization of scratch reexes In the 19th and rst half of the 20th century, the spinal cord was considered, besides as a conductive structure, primarily as a reex machine. The application of the term reex to such acts seems to have been made rst by Descartes (1649), on the analogy of the reection of light, the sensory effect in these cases

tion or perception. In this sense, proprioceptor is clearer by referring to the peripheral sensory receptors (proprio-receptor). Proprioceptors are classically dened as being activated by mechanical stimuli arising from the bodys selfgenerated motor actions [94,140,339]. Prochazka [299] subsumes under this rubric all the receptors that carry signals related to these variables, irrespective of whether the signals reach consciousness or contribute to movement control at subconscious levels. Proprioceptors comprise a fairly wide group of different mechano-receptors, from muscle receptors (muscle spindles, Golgi tendon organs, arguably some mechanically excitable free nerve endings), joint and ligament receptors, to cutaneous mechano-receptors, which can be excited by stimuli impinging on them from both the exterior and interior world, thus being both exteroceptors and proprioceptors.

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being reected back, so to speak, as a motor effect ([150], p. 141). The optic analogy suggests a deceiving simplicity, which illusion appears to have survived until today. Indeed, it may apply in case of the articial tendon reex used by hammering neurologists to test the excitability of the spinal cord, and in case of the even more articial, and most popular, H-reex [291,324]. Natural reexes can be complex, however, and their careful analysis reveals problems, which the spinal cord has to solve by means that in many respects involve proprioceptive feedback. Consider a seemingly simple behavior, namely the frogs wiping reex. When a spinalized frog is put on a platform with three legs xed and only the right hindleg free to move, and a small piece of paper soaked with acid is put on the right forearm, the right hindleg will perform a sequence of movements aimed at removing the noxious stimulus. First, the toes of the hindleg are placed close to the stimulus (positioning or postural component), then the paper is whisked away (extension movement), followed by another exion movement bringing the toes back close to the stimulus, and these latter two phases may be repeated in a rhythmic fashion depending on the success of the rst whisking phase. This complex movement pattern in space and time, composed of several distinct components, can be adapted to varying external circumstances such as the position of the stimulus, and the frogs body conguration [23,105,176,295,331]. Similar features characterize the scratch reex of the spinalized turtle [350]. A bit more complicated is the cats or dogs scratch reex [194]. Suppose, for example, a standing cat is irritated by a stimulus on one pinna. The cat will lift an ipsilateral hindleg diagonally toward the head by a combination of hip and ankle exion with knee extension (approach), while part of the body weight is shifted to the other legs, thus stabilizing the body. The scratching limb then falls into a sequence of 160 oscillations at a frequency of 48 Hz. Scratching is performed most often in a sitting posture and sometimes in a lying or standing position, with different initial conditions for the following dynamic motor act [194]. Even spinalized cats can perform paw shakes, indicating that the basic underlying functions are organized in the spinal cord [317]. Furthermore, spinal cats can execute paw shakes simultaneously with walking. Although the frequency of stepping is reduced in this condition and stance is shortened and swing prolonged, the spinal cord is capable of organizing the two behaviors simultaneously [49]. This suggests that the two behaviors are organized by different central pattern generators (see below), which must be coordinated, of course. Overall, the motor task of the nervous system and its skeletomuscular instruments consists of localizing the initializing stimulus and converting it into a kinematic trajectory of the limb endpoint by generating the appropriate kinetics. Conceptually, this motor act can be broken down into a series of events, with multiple feedback effects: Excitation of appropriate sensory receptors. Obviously, in the scratch reex (and similar reexes), cutaneous sensory receptors are rst excited to get the reex going. Even before

movement onset (due to possible fusimotor effects on muscle spindles) and when the movement is underway, proprioceptors change their discharge and inuence the progress. Generation of initial posture and postural adjustments. As described above, the scratch reex may start from different initial postures that must be generated and appropriately adjusted for the reex as well as secured against external disturbances (Section 10). Rhythmogenesis. The rhythmical component of the scratch and wiping reexes and other rhythmical movements depend on central rhythm generators (Section 3). Sensory-motor transformations. The entire motor act involves various transformations: Localization. The localization of stimulus and goal must be represented within the central nervous system (CNS) in some bodily reference frame, which is usually referred to as a body schema, in whose construction proprioceptors play an important part (Section 10). Spatial transformations. Target-oriented movements require the determination of target location with respect to the moving body part, in wiping and scratch reexes as well as in voluntary arm reaching. Different functional elements of the reex-generating system work in different frames of reference, however. Thus, cutaneous receptors are arrayed in a two-dimensional sheet folded in three-dimensional space; each fusiform muscle develops forces essentially in an intrinsic one-dimensional direction; joint angles span an intrinsic one-dimensional to three-dimensional space (depending on joint type: hinge to ball-and-socket joint); endpoint movement occurs in an extrinsic three-dimensional space; and the elicited proprioceptor activities are specied in an intrinsic one-dimensional to three-dimensional space (depending on receptor type). These different representations require spatial transformations between the frames of reference (Section 13). Kinematic-to-kinetic and kinetic-to-kinematic transformations. Sensory inputs are, at least to some extent, cast in kinematic terms related to movement, while muscle activities achieve kinematic goals in terms of kinetic (dynamic) variables related to forces. This requires kinematic-tokinetic transformations, generating the daunting inverse dynamics problem [295] (Section 13). Conversely, the goal of muscle activations is a movement trajectory in external space, implying that muscle forces must be transformed into muscle torques, these into (compound) joint torques (inuenced by other torques such as gravitational and inter-segment interaction torques; Section 11), these into joint-angle changes, and these into a paw movement [406]. This sequence of events (with inherent feedback effects) must be taken into account by the spinal cord. Musculo-skeletal properties. Some problems the CNS has in executing movements arise from the complex properties of the peripheral musculo-skeletal system. Muscle operation is exquisitely nonlinear, dependent on activation history and on a muscles linkage to bones, which must be taken into account

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by the CNS in organizing neural commands to muscles (Section 5.5). Stabilization. Several inherent properties render the neuromuscular system prone to various types of oscillatory instability, which must be controlled by the CNS (Section 6). Muscle fatigue is an inherent property of the neuro-muscular system, which must be kept in check as far as possible (Section 7). Multi-joint coordination. Posture and movement are executed by multi-joint systems, which pose much more severe problems than single-joint systems (Sections 911). Redundancy reduction. There is no unique mapping of jointangle congurations onto end-point locations, which causes a redundancy problem (Section 9). Adaptability and plasticity. Neuro-muscular systems must be able to adapt to changing environments, requiring plasticity of neuronal networks (Section 12).

This list contains sub-functions, most of which have been claimed to involve proprioceptive feedback in some way. The list will serve as a guideline of the following discussion, which will take a more general view and transcend the particular paradigm of the wiping or scratch reex, however. 3. Rhythmogenesis In order to produce the rhythmic scratch-reex component as well as other rhythmic movements (e.g., locomotion, mastication, respiration), the CNS makes use of complex networks of neurons, which are generally called central pattern generators (CPGs) [185]. While in principle they may produce rhythmic motoneuron activities without sensory feedback and signals descending from supraspinal structures, these inputs shape the timing and magnitude of motoneuron activities, and their processing is conversely inuenced by CPGs [14,130,128,280,282,317,355]. The organization and operation of CPGs will be mentioned only in passing. Rhythmic pattern generation. Conceptually, locomotor CPGs may be divided into [40,120,160,202,320,321]: Rhythm-generating networks (clocks). The rst requirement is the existence of a clock or clocks to provide for the fundamental frequency of the rhythm. As a matter of fact, this frequency must be variable to accommodate the different gaits. Pattern-formation networks shape excitatory and inhibitory neuronal waveforms and distribute them in various combinations to the different skeleto-motoneuron2 pools so as to generate coordinated muscle activation patterns. This is a non-trivial task because the spatio-temporal muscle
Skeleto-motoneurons innervate the (extrafusal) large muscle bers in skeletal muscles doing the main muscle work. In mammals, skeleto-motoneurons are divided into pure skeleto-motoneurons called -motoneurons, which do just that, and -motoneurons that innervate extra- and intrafusal muscle bers in muscle spindles. For simplicity, we will refer to both classes as -motoneurons.
2

activation patterns need to be tailored to the peripheral biomechanics of the limb and the muscles acting on it. Conceptually, therefore, the coordinating network incorporates an internal model of the peripheral musculo-mechanical system. Adjustment and adaptation to prevailing circumstances. The locomotor activation patterns must be implemented in and adapted to a complex and dynamically changing environment [73,281,282,317]. The actual circumstances include external properties, such as terrain, surface properties, obstacles, qualities of the medium (air, water, ground, surface), additional forces and resistances (e.g., wind), and internal properties of the moving body, such as musculo-skeletal and nervous properties and perturbations. The actual muscle activation patterns must therefore be properly adapted by sensory feedback, including muscle proprioceptive and cutaneous signals [73,282,317]. The importance of sensory feedback is indicated by the fact that cat locomotion is more normal and stable, less fatiguable and more easily adjustable to a wider range of speeds with than without intact sensory feedback [129,299]. This applies more generally to other motor activities including voluntary goal-directed and manipulative movements, which become severely disturbed after de-afferentation [116] (Section 11.3). Moreover, when a swinging leg hits an obstacle on the foot dorsum, the movement should not be carried through at all cost, but changed so as to allow the foot to circumvent the obstacle. This requires that cutaneous/proprioceptive signals inuence (reset, re-program) the locomotor CPG. Conversely, the signicance of various sorts of sensory signals changes with the specic task (stance, walking, running, etc.) and, within each task, with the phase of the cycle, during which the bodyenvironment relation is changing dynamically. Hence, any reexes and other motor activities based on sensory signals should also change in a way adapted to the instantaneous conditions. This requires that reexes be plastic rather than immutable. In fact, all known spinal reex pathways are modied during locomotion by way of various mechanisms [71,73,248,280,282,317,410].

4. Generation of upright body posture During upright stance of animals suspending their body above the ground by means of legs, the controlling neural system should meet the following general requirements: Anti-gravity function [236]: Generation of upward thrust by provision of muscle tone in anti-gravity muscles. Balance. Under stationary conditions of upright stance, the projection of the bodys center of mass must fall within the base of support. Coordination of proper muscle torques across the series of limb, trunk and neck joints. Stabilization of posture against de-stabilizing inuences. Posture can be perturbed by acceleration forces resulting from:

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Internal perturbations. Breathing, heart beat, neural noise, muscle tremor (Section 6.2), muscle fatigue (Section 7). Movements of other body parts through inertial interaction forces. While standing, movements of body segments such as an arm will change the distribution of body mass as well as exert inertial interaction forces between the body segments (Section 11). In order to preserve equilibrium, the CNS must take these actions into account in advance, in a way precisely calibrated to movement direction and velocity (Section 10.6). External inuences, including gravity and interactions with the environment (e.g., changes in support, sudden bus stops, pushes to the body, sudden obstacles). Estimation and prediction of the multiple types of forces acting on the body, including its own muscle forces, gravitation, inertial interactions between segments, friction between segments and between body and environment, and their interactions [146]. This requires the use, processing and integration of vestibular, proprioceptive and cutaneous afferent signals. Central representation of an appropriate posture in terms of a postural body schema, including a representation of the bodys conguration and its relationships with the external world (Section 10.2). There are a number of means for the body to solve the above problems. The central role is occupied by the CNS, which must orchestrate and produce muscle forces so as to complement and coordinate all other forces acting on the body [146]. These functions depend signicantly on proprioceptive feedback. 4.1. Generation of anti-gravity thrust and stiffness To keep terrestrial animals and humans upright on their legs requires mechanisms to resist external disturbances, including gravity. This stiffness is provided by at least three mechanisms [81,146,147,148,239]: Contributions from skeleto-articular elements. For example, in humans and large quadrupeds such as elephants and giraffes, upright stance is supported to a considerable extent by the anatomical alignment of limb segments, thus engaging connective tissues to provide the required stiffness while minimizing muscular forces [146]. Visco-elastic properties of passive muscles provide (small) stiffness and automatic compensation for load changes during weight bearing. Continuing muscle activity, which can be minimized, however, by skeleto-articular contributions. In smaller quadrupeds such as dogs and cats, the hindlegs are fairly exed, whereby larger muscle forces are needed to maintain the relative extension against the exing forces due to gravity [146]. Tonic muscle contraction renders the muscle more resistant to extension according to its lengthtension characteristics. In cats, the range of soleus muscle lengths during quiet standing and locomotion covers the steep part of the lengthtension curve [239].

Sensory feedback and associated central control systems help regulate limb biomechanics and stance. Reex-mediated stiffness results from the actions of the stretch reex (below), which recruits additional -motoneurons and increases the ring rate of already active -motoneurons. This feedback is primarily related to load or force and acts to enhance muscle extensor activity (Section 5.7). The rst three mechanisms are the fast-acting rst line of defence, providing a load-compensation mechanism and thus reducing postural sway and yield to gravity during quiet stance. Reex-mediated stiffness may add to the rst defence, but at a latency depending on conduction, synaptic and contraction delays. The brunt of the active muscle work has to be carried by the physiological limb extensor (anti-gravity) muscles, which once active also provide for most of the stiffness. This is well illustrated by the phenomenon of decerebrate rigidity, which will be used as a heuristic primer. 4.1.1. Decerebrate rigidity Exaggerated limb extensions occur under a variety of pathological circumstances, particularly in decerebrate rigidity. In this state, the animal (usually cat or dog) extends its limbs, the neck and tail, to the extent that the activity in anti-gravity muscles is strong enough to enable upright stance (review of early literature: [123,239]). On a much-simplied view, there are two experimental paradigms producing decerebrate rigidity. Anemic decerebration [293] produces extensor muscle activity predominantly by a hyper-activity of -motoneurons, whereby it is classically referred to as -rigidity [123,239]. The second type [338] appears when the brainstem of a cat or dog is severed at the intercollicular level of the midbrain, and is characterized by an additional increase in -motoneuron activity, thereby called gamma type of rigidity ([123], p. 165). Note that both types of rigidity provide for both anti-gravity upward thrust and stiffness. Sherringtons [338] classical decerebrate posture has been interpreted as reex standing. Sherrington showed that the underlying mechanism is associated with exaggerated extensor stretch reexes. An immediate question about the stretch reex is which of the various receptors in muscle is responsible for it? Liddell & Sherrington wisely refrained from comment on this . . . ([239], p. 421). 4.1.2. Core stretch reex circuit The simplest possible reex mechanism is based on muscle stretch-sensitive sensory receptors and their monosynaptic contacts with homonymous -motoneurons. Such a mechanism appears fundamental in being phylogenetically ancient. Although arthropods, amphibia and mammals use different types of proprioceptors, they use similar organizational principles in that proprioceptive organs lie in parallel to skeletal muscle bers and excite homonymous motoneurons. This circuit has been interpreted as a postural negative feedback (that) helps to maintain a given position ([58], p. 199). The

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stretch receptors in mammals differ signicantly from those in invertebrates, however. In vertebrates, the stretch-sensitive muscle receptors with monosynaptic connections to motoneurons are the muscle spindles [19,299]. (Among stretch-sensitive receptors are also Golgi tendon organs and some non-muscular cutaneous mechanoreceptors to be dealt with later.) Evolutionarily, muscle spindles appear in anurans (frogs and toads). In these, each spindle has only one sensory ending whose afferent ber makes monosynaptic contacts with motoneurons [342]. The mammalian muscle spindle is more complicated in having two types of sensory ending and associated afferent: the primary ending with its group Ia afferent and the secondary ending(s) with group II afferent(s) [19]. Their monosynaptic connections to -motoneurons are of different strength (below). In mammals, then, the simplest stretch-reex circuit that could provide for stretch-mediated stiffness consists of monosynaptic connections from group Ia afferents to homonymous -motoneurons, as illustrated in Fig. 1. (For the ontogenetic development of this circuit, see ref. [51], and for a detailed functional anatomy of Iamotoneuron connections, see ref. [220].) In parallel, there exist oligosynaptic linkages (see below). In general, the strongest monosynaptic Ia-connections exist with -motoneurons involved in postural tasks, particularly those innervating anti-gravity muscles, and in these cases an inverse relationship holds between monosynaptic Ia excitatory postsynaptic potential size and the size of the -motoneurons. Thus, those motor units, which are predominantly active during postural tasks (S-type units with small -motoneurons [38]), receive the strongest monosynaptic Ia afferent feedback [361]. Group II afferents from secondary muscle spindle endings make a smaller monosynaptic contribution to -motoneuron excitation and might thus support the monosynaptic group Ia actions [186,239,349]. Moreover, excitatory oligo- or polysynaptic connections might contribute their share [239]. Otherwise, group II afferents produce a bewildering variety of reex actions [164,329], which will be dealt with below (Sections 5.7.4 and 9.4.5). Sherringtons reex standing could come about as follows. First, after decerebration the activity of the vestibulospinal tract descending from Deiters (lateral vestibular) nucleus is enhanced, thus generating an augmented excitatory drive to extensor -motoneurons and increasing extensor muscle tone. Second, the vestibulospinal tract excites, besides -motoneurons, the associated homonymous -motoneurons, whose enhanced activity provides excitatory bias to the spindles, which in turn reexly excite -motoneurons and thus enhance extensor muscle activity indirectly. This enhanced static tone per se provides for increased stiffness (resistance to change). Third, the strong stretch reex action adds to resistance against disturbances. Thus, when an extensor muscle slightly yields under the impact of body weight or an accidental internal decrease of muscle tension, its muscle spindles are stretched, raise their discharge rate and reexly excite their homonymous -motoneurons, which thus increase anti-gravity muscle contraction to resist the yield. This gamma type of rigidity ([123],

Fig. 1. Schematic diagram of the monosynaptic stretch reex circuit for cat hindlimb muscles. Each neural element represents a population. Excitatory neurons are symbolized by open circles and their synapses by T junctions. At the bottom, a hindleg is sketched with outlines of the ankle exor muscles (left) and ankle extensor muscle (right). The muscles contain muscle spindles symbolized as straight lines with coils (primary sensory endings) around their middle portions. Spindles lie in parallel to the main skeletal muscle bers. They receive a motor innervation from -motoneurons and from branches of -motoneurons (here called -motoneurons, see footnote 2). Group Ia afferents originate from primary endings on muscle spindles and project to the spinal cord, in which they make monosynaptic excitatory connections to -motoneurons of their own (homonymous) muscle and of synergistic muscles (Section 9.4.4). - and motoneurons receive a variety of excitatory and inhibitory inputs from segmental sensory, propriospinal and supraspinal sources, symbolized by the dashed arrows on top.

p. 165) should therefore depend on an intact reex loop, which indeed it does, since severance of the dorsal roots abolishes much of the rigidity [239]. Sherrington [340] summarized his view of reex standing in decerebrate cats as follows: A peculiarity which distinguishes the stretch reex from other reexes is that . . . the stretch reex excites in its limb just the one muscle stretched. The reex standing of the limb is a harmonious congeries of stretch reexes, each component reex being the self-operating reaction of an individual extensor muscle (p. 929). This quotation contains two interesting ideas. First, stretch reexes are here considered as devices to stabilize muscle length in quiet stance. Second,

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stretch reexes appear as self-operating reactions of individual extensor muscles. The importance of muscle spindles for posture and movement has recently been underscored by neurotrophin-3-decient mice that are unable to support their weight and exhibit unnatural postures due to an absence of muscle spindles and proprioceptive afferents in their limbs [93,375]. For unknown reasons, some classically decerebrate preparations may temporarily exhibit rigidity predominantly in exor muscles. Furthermore, in the acute spinal cat, the injection of dihydroxy-phenylalanine (DOPA) may enable tonic stretch reexes in both exor and extensor muscles [239]. Finally, while standing on a slippery surface (e.g., ice), humans assume a safety stance, in which they stiffen their legs by extensor-exor coactivation. It may thus be expected that monosynaptic reex circuits also exist in limb exor muscles, which is the case. 4.2. Reciprocal Ia inhibition There are situations when exor muscle activity has to be coordinated with extensor activity. If a perturbing stretch of an extensor muscle elicits its autogenetic reex contraction, this would stretch the antagonist muscle(s) and elicit an antagonist stretch reex. In order to prevent this from happening (which could lead to a cascade of agonistantagonist contractions), -motoneurons to antagonist muscles should be reciprocally inhibited simultaneously with the stretch-evoked activation of agonists. Thus, as schematically illustrated in Fig. 2, a second important spinal connection of muscle spindle group Ia afferents is onto segmental lamina VII interneurons that inhibit antagonist -motoneurons (and some cells of origin of the ventral spinocerebellar tract (VSCT), not illustrated) [164]. Reciprocal inhibition may have an undesired side effect. When extensor muscles are activated and shorten, the antagonist exor muscles are stretched. Thereby exor group Ia afferents increase their ring rate, excite their homonymous -motoneurons and reciprocally inhibit the extensor -motoneurons, which may interfere with the extensor action and impair alternating movements, in particular. This side effect can be prevented by in turn inhibiting the exor-coupled Ia interneurons by their opponents, introducing mutual inhibition (Fig. 2). Mutual inhibition is a fairly common mechanism among some sub-populations of spinal interneurons [18,164,165,329]. 4.3. Recurrent inhibition The preceding discussion might suggest that, quite generally, the evolution of one neuronal circuit may create a side effect whose removal would call for another circuit. Along this line of thinking, recurrent inhibition has been suggested to solve a problem introduced by reex actions of muscle spindles and their fusimotor control. Thus, recurrent inhibition has been hypothesized to localize the stretch reex [37], to counteract the effects of uctuations in fusimotor bias to muscle spindles [123] or to limit the extent of group Ia excitatory effects on -motoneurons [178]. Whether, as compared to scientists, evolution thinks

Fig. 2. Simplied diagram of monosynaptic excitation and reciprocal inhibition evoked by muscle spindle group Ia afferents. Excitatory neurons are symbolized by open circles and their synapses by T junctions. Inhibitory interneurons and their synaptic terminals are symbolized by large and small lled circles, respectively. Same scheme as in Fig. 1, supplemented by reciprocal inhibition from exor group Ia bers to extensor -motoneurons, and vice versa. Note that reciprocal Ia inhibitory interneurons (Rec Ia inh IN) mutually inhibit each other.

this way, is debatable (Section 9.4.8.3). In any case, such reasoning puts recurrent inhibition in close functional association with the stretch reex. Moreover, recurrent inhibition appears to have evolved together with mammalian muscle spindles, their system of two afferents and -innervation [158,387,391]. Another functional association between recurrent inhibition and the muscle proprioceptive system may be construed as follows. Skeletal muscles generate movements by developing forces against the prevailing loads, entailing muscle-length and joint-angle changes. Changes in muscle length in turn codetermine muscle force via the well-known forcelength and forcevelocity dependencies [279]. For control purposes, these two important state variables had best be fed back to the central controllers. In addition, muscle force is determined by its activation via -motoneurons. Thus, in a recent model of the neuro-musculo-skeletal system of the cats hindlimb, Loeb et al. [216,217] suggested that -motoneurons receive feedback signals of three pertinent state variables: muscle force, muscle length and an estimate of muscle activation. In this scheme, Renshaw cells were suggested to provide an efference copy of motor output used to estimate the muscle activation or force component generated by neural excitation [216,217,388391].

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Another line of research associates recurrent inhibition with anti-gravity functions in stance. 4.3.1. Prevalence of recurrent inhibition Emphasis is here put on the occurrence and distribution of recurrent inhibition among limb -motoneurons (for details see refs. [18,178,391]). (i) The strength of recurrent inhibition in the cat hindlimb shows a gradient, becoming weaker in from proximal to distal muscles. An even stronger such gradient has been revealed in the cat forelimb [391]. Such gradients are also apparent in humans, where they can be inferred using various techniques based on electrical nerve stimulation and their effects on motor unit discharge patterns and Hreexes [178]. The patterns in humans differ somewhat from those in cats, which may be expected from the different functional roles of cat and human forelimbs. Thus, recurrent inhibition is weak or absent in -motoneuron pools concerned with precise, distal limb movements, i.e., in hand muscles in cat and man [178,391]. This distribution exhibits some interesting associations with distributions of other systems. In particular, at least in the cat forelimb, the distribution of recurrent inhibition is associated with an inverse distribution of -innervation in muscle spindles. The -motoneurons of distal muscles involved in ne manipulative movements lack recurrent inhibition and have a high degree of -innervation, suggesting a different fusimotor regime. Recurrent inhibition is strong among -motoneurons of more proximal muscles playing a greater role in posture and locomotion, which muscles also have a lower degree of -innervation, relaying a greater role to -fusimotor control and thus associating recurrent inhibition with -fusimotor control [158]. There is another association with effects of descending spinal tracts. The dorso-lateral system consisting of the cortico- and rubrospinal tracts is more important for skilled movements of the hand, while the ventro-medial system including the reticulo- and vestibulospinal tracts make a greater contribution to movements in proximal joints during locomotion [52]. How these correlated distributions are functionally related needs to be determined. Especially, the phylogenetic persistence of -innervation in mammals remains a vexing problem for functional interpretation [356]. (ii) Within this general framework, recurrent inhibition appears to be particularly strong in and between -motoneuron pools that are active during the stance phase of locomotion and during quiet upright stance. It ts with this pattern that recurrent inhibition mediated by Renshaw-like interneurons is present in the chick spinal cord, i.e., in a two-legged bird [379,403]. (iii) There is also recurrent facilitation between -motoneurons, probably mediated via recurrent inhibition of reciprocal Ia inhibitory interneurons and of Renshaw cells. This facilitation does not show a topographically organized distribution as existing in recurrent inhibition, and it extends further rostro-caudally [250].

Fig. 3. Simplied diagram of recurrent inhibition. Same scheme as in Fig. 2, supplemented by recurrent inhibition via Renshaw cells, and mutual inhibition between Renshaw cells. Renshaw cells, which receive their main excitatory input from -motoneurons, inhibit homonymous and synergistic - and motoneurons, reciprocal Ia inhibitory interneurons excited from homonymous and synergistic group Ia bers, and other Renshaw cells, in particular those predominantly but not exclusively related to antagonist -motoneurons (mutual inhibition).

4.3.2. Core recurrent inhibitory circuits As schematically illustrated in Fig. 3, intraspinal recurrent motor axon collaterals make excitatory synapses on Renshaw cells, which in turn inhibit [18,154,164,178,388,391]: -Motoneurons; -Motoneurons belonging to the same and synergistic motoneuron pools; Reciprocal Ia inhibitory interneurons receiving monosynaptic excitation from homonymous and synergistic muscle afferents. The functional rationale could be that, since Renshaw cells inhibit -motoneurons, they should also inhibit associated reciprocal Ia inhibitory interneurons with the same group Ia inputs; Other Renshaw cells (mutual inhibition) which are particularly, but not exclusively, related to antagonistic -motoneurons; Some cells of origin of the ventral spinocerebellar tract (VSCT) receiving monosynaptic excitatory input from group Ia afferents (not shown).

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5. Muscle proprioceptive feedback and recurrent inhibition in action So far, the discussion has concentrated on stationary stance conditions. Now the question arises as to the behavior and role of muscle proprioceptive feedback and recurrent inhibition in dynamic movements. 5.1. Muscle spindles and Golgi tendon organs in action During movements, the inputs to muscle spindles and Golgi tendon organs change. But their outputs are differently related to their respective inputs. 5.1.1. Golgi tendon organ discharge in action For the sake of comparison, we shall start with Golgi tendon organs. Since they are located at the musculo-tendinous junctions, they respond very sensitively to the forces developed by the muscle bers inserting into them and, to a lesser extent, to passive forces developed during muscle stretch [163,299,304]. Their discharge in naturally behaving cats appears simply related to muscle force [301]. The averaged afferent activity from ensembles of tendon organ afferents from the triceps surae muscle were fairly well correlated with the electromyographic activity and agreed well with separate triceps surae force measurements in normal cat locomotion, supporting the notion that ensembles of tendon organ afferents signal whole-muscle force [301]. Similarly, in humans, Golgi tendon organ afferent ring rate was highly modulated during active movements, monitoring the amount of muscle force [3]. 5.1.2. Muscle spindle discharge in action By contrast, muscle spindle afferent discharge is more complicated. While in amphibians the activation of extrafusal and intrafusal muscle bers is coupled by -innervation, the existence of -motoneurons in mammals opens up a new dimension of freedom, at least principally. (In some muscle territories, muscle spindles may also receive sympathetic inputs [309].) Why are there -motoneurons in addition to - and -motoneurons, with these classes of motoneurons also having different sizes and structures [263]? The evolution of -motoneurons would appear to make functional sense only if they exhibit activity patterns not closely coupled to those of -motoneurons, and thus receive inputs independent of those to -motoneurons. The study of this issue in animals and humans has led to vividly debated concepts. 5.1.3. Follow-up length servo hypothesis After early studies on the physiological actions of motoneurons [123,239], and with the spread of control engineering ideas in physiology, Merton [253] proposed a concept that was explicitly based on -fusimotor spindle innervation. In this view, the feedback system set up by muscle spindle group Ia afferents and their monosynaptic connections to homonymous -motoneurons would be used as a servo system. In slow and precise voluntary movements, in which the

inevitable signal-transmission delays around the loop are not that signicant, the motor commands descending in the spinal cord would impinge primarily on the -motoneurons. These would then activate muscle spindles, which in turn would reexly activate -motoneurons to cause a muscle contraction. This concept could also be applied to locomotion, with the locomotor CPG supplying the motor command. Mertons idea was an early expression of the notion of internal model, in which the muscle spindle acts as a forward model of skeletal muscle [390] (see also below). The model was easily understandable. Mertons concept led to much valuable research even though it did not stand the test of time. The quality of performance of a servo-mechanism critically depends on the power amplication in the loop, that is, the loop gain. For a good suppression of disturbances, the loop gain has to be high. In subsequent studies incited by Mertons concept, it has turned out that the stretch reex gain measured in animals and humans on average is modest in most circumstances, albeit modiable and dependent on input amplitude. Moreover, in humans, the activation of -motoneurons was found not to precede that of -motoneurons, which would have been required by Mertons hypothesis. Ever since, strict servo control of muscle contraction has fallen from grace [214]. 5.1.4. Servo-assistance hypothesis In humans and animals, many movements are produced by the concurrent activation of both - and -motoneurons, as in Sherringtons standing decerebrate cat (Section 4.1.2). The servo-assistance hypothesis, in its strict version [239], proposes that the primary activation of a muscle occurs via its -motoneurons, whose activation is then supported by feedback from muscle spindle afferents being excited, in parallel, by motoneurons. The idea is that fusimotor action should provide a temporal template of the intended movement so that, if this proceeds undisturbed, spindle discharge should ideally be constant. The implied offset of the effects of muscle length changes on spindle discharge had best be provided by static -motoneurons, whereas dynamic -motoneurons could be differentially activated according to motor task whenever it would be necessary to ensure a high muscle spindle sensitivity to imminent muscle length disturbances. This scheme is akin to a model-reference system in which an internal model (muscle spindle) is put in parallel to the plant (skeletal muscle) that the model is supposed to mimic. As long as the movement proceeds according the desired trajectory represented in the fusimotor signal, the two outputs (intrafusal muscle ber lengths and extrafusal muscle ber lengths) should match. If not, the difference should be signaled by spindle afferents [148,387,390]. The actual discharge patterns of muscle spindle afferents during movements in humans and animals have turned out not to be quite as simple as required by the servo-asistance hypothesis, as briey summarized now. 5.1.5. - and -motoneuron discharge patterns in action Despite many physiological studies in animals and humans, the question of exactly how, during motor acts, -motoneurons are activated in relation to -motoneurons has not yet been

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settled unequivocally [87,151,265,301]. This is due, in part, to the different movements investigated and different preparations and recording methods used. The movements studied range from routine rhythmic locomotion and other rhythmic movements (respiration, mastication), reex movements (e.g., scratch reex) to voluntary movements. The preparations employed have varied from awake, freely moving animals to acute reduced preparations of various sorts. And the recordings have been obtained from unidentied or identied -motoneuron efferents or from muscle spindle afferents in awake cats, where fusimotor inputs could be estimated only indirectly. Since, in the cat, the fusimotor effects on muscle spindles can be functionally divided into static and dynamic ones, there are at least four types of fusimotor effects: static and dynamic -, and static and dynamic -innervation (the dynamic -motor units being of type S and the static -motor units of type F), mediated via three types of intrafusal muscle bers (bag1 , bag2 , chain bers). Furthermore, some authors suggest a functional division of static fusimotor effects via bag2 and chain bers [364]. Whether this diversity is exploited to the fullest extent under physiological conditions is unknown, although this to occur has been suggested for cat locomotion [87]. In particular, the selective supraspinal control of the various types of -motoneurons is still at issue. Studies performed on respiratory, masticatory and limb muscles in cats and other animals have yielded diverse, in part contradictory results. During respiration in cats, the discharge from muscle spindles residing in inspiratory and expiratory muscles increases when their parent muscle is contracting and decreases during muscle relaxation [65], suggesting that and -motoneurons re concomitantly, otherwise spindle afferents would be silenced during muscle contraction. Indeed, direct recordings have shown that - and -motoneurons do re concomitantly, with the exception of some -motoneurons remaining unmodulated [334]. Similar spindle discharge patterns are seen during masticatory movements. In lightly anesthetized cats, spindle afferents from jaw-closing muscles increase their ring rate during active muscle contraction, but are silenced during the same movement imposed passively [360]. During normal locomotion in intact cats, the discharge rates of muscle spindle afferents from hindlimb muscles are modulated deeply due to changing muscle length and fusimotor inputs. In addition, the precise spindle discharge pattern depends on the particular parent muscle and its type of contraction during movement [213,265,299,301]. The ring rate proles of spindle afferents from hamstring muscles could be predicted fairly well from the length and velocity signals alone. By contrast, the ring proles of spindle afferents from the triceps surae muscles deviated from the predicted proles, particularly during electromyographic activity, indicating that the components of fusimotor action correlated with extrafusal muscle activity were signicant in triceps surae, possibly because this muscle is more strongly recruited in the cat step cycle [301]. An important question is which type of fusimotor neuron does, or does not, modulate its discharge in parallel to motoneurons. A number of combinatorial patterns have been suggested. For example, in some cases, such as the fusimotor

outow to the medial gastrocnemius muscle of high decerebrate cats during locomotion, part of the fusimotor outow (S , type 1) has a temporal prole resembling the active unloaded shortening of the parent (medial gastrocnemius) muscle and may thus serve as a temporal template of the intended movement, while other parts (S , type 2, and D ) may serve other functions, the dynamic -motoneuron (D ) pattern possibly sensitizing the group Ia afferents to detect the onset of muscle lengthening and departures from the intended movement trajectory [362,363,365]. In humans, modulating inputs to the fusimotor system have usually to be inferred indirecty from effects on the discharge of muscle spindle afferents, which can be recorded by microneurography. Such inferences are usually compromised by a very restricted range of movements that can be studied without jeopardising the recording stability (virtually excluding recordings during locomotion), and by the common inavailability of recordings of intrafusal length changes. The discharges of muscle spindle afferents show varying patterns during various voluntary or reexly elicited muscle contractions. On the one hand, group Ia afferent discharge hardly changed during a precision nger movement that tracked a trapezoidal waveform on the oscilloscope screen and caused length changes of the muscle containing the spindle [152]. This is in keeping with Matthews servoassistance hypothesis (Section 5.1.4). On the other hand, muscle spindle afferents have been seen to modulate their discharge rate with movement. For example, most muscle spindle afferents from the extensor digitorum muscles of the forearm exhibited a stretch response while the subjects performed alternating movements of moderate speed at the appropriate metacarpophalangeal joint, and in response to imposed movements of similar amplitudes and velocities. Hence, in general, human muscle spindles monitor muscle length and velocity in routine movements of moderate speed as long as opposing loads are small [3]. In conclusion, simple schemes, such as the servo-regulation of a single muscles length or stiffness are no longer viable [214]. Inevitably, more complex concepts are called upon, which most likely need to take account of the diverse biomechanical actions that different muscles may have. It is well conceivable that different motor tasks require different fusimotor activation patterns in relation to skeletomotor activation patterns. For example, whether during rhythmic movements the discharge of static or dynamic -motoneurons is rhythmically modulated with -activity may be functionally related to whether the muscle innervated by them undergoes shortening (concentric), lengthening (eccentric) or near-isometric contraction [265]. In cats, the masseter, medial sartorius and tibialis anterior muscles shorten when active and receive phasic static fusimotor activity, thus maintaining or increasing group Ia afferent discharge depending on shortening velocity in accordance with the servo-assistance hypothesis. On the other hand, phasic dynamic fusimotor activity has been observed in muscles such as the triceps surae during locomotion and external intercostal muscles during respiration, these muscles undergoing lengthening contractions while active. Increased dynamic spindle sensitivity could then counteract lengthening by supporting the active muscle via the monosynaptic Ia afferentmotoneuron

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connection. The function of tonic fusimotor discharge patterns is less clear [265]. 5.1.6. Supraspinal and sensory inputs to - and -motoneurons Since -motoneurons communicate the CNSs commands to skeletal muscles, they must receive all kinds of inputs from descending tracts and sensory afferents (Fig. 1) in order to fulll their multifarious roles in various motor acts [18]. Traditional descending systems include the cortico-, rubro-, reticulo-, vestibulo-, tecto- and interstitiospinal systems, which terminate mono- or polysynaptically on -motoneurons in differentiated patterns depending on muscle type (e.g., exor or extensor), position (e.g., proximal of distal in limb), and motor unit type [36,52,373]. In cats, monkeys and humans, parts of the descending commands to forelimb -motoneurons are mediated via cervical propriospinal interneurons, which also receive cutaneous and muscle afferent signals [5,6,290]. Furthermore, there are complex descending pathways arising from the limbic system, hypothalamic nuclei, locus coeruleus and raph e nuclei, the latter two exerting neuromodulatory noradrenergic and serotonergic effects on various spinal neuronal systems [52,108,144,162] (Section 7.2.3). Finally, -motoneurons receive direct or indirect projections from sensory afferents in all groups (IIV) (see below). Since -motoneurons exhibit discharge patterns that in part diverge from those of -motoneurons, they, too, must receive various inputs that differ in part from those of -motoneurons [151,387]. 5.2. Modulation of segmental sensory input by presynaptic inhibition While muscle spindle feedback during movement might appear to be controlled, by fusimotor systems, in a way sophisticated enough to subserve varying demands of various motor tasks, it is further complicated by a phylogenetically ancient system at its very entrance to the spinal cord, namely presynaptic inhibition, acting via inhibitory GABAergic interneurons (see Fig. 4) and producing primary afferent depolarization in sensory afferent terminals, which may at times give rise to antidromic action potentials in sensory afferents [18,154,164,317,318,329,383]. Related to locomotion, presynaptic inhibition modulates the synaptic efcacy of spindle group Ia and II, tendon organ Ib and cutaneous afferents [317,351]: State- and task-dependent locomotor-related modulation. As compared to non-locomotor states in cats, the synaptic transmission from group Ia afferents to -motoneurons is suppressed by an augmented tonic presynaptic inhibition, starting with, persisting throughout and outlasting the ctive locomotor activity [121]. This also holds for other sensory afferents, such as those from muscle spindle group II afferents [248]. This depression of synaptic transmission in group Ia and II spindle afferent pathways may contribute to the reduction of H- and stretch reexes during locomotion [317].
Fig. 4. Simplied diagram of inuences exerted by groups IIIIV afferents from extensor muscles on spinal moto- and interneurons. Also included are some pathways from extensor group Ib afferents from Golgi tendon organs, which during rest inhibit extensor -motoneurons and facilitate exor -motoneurons (via inhibitory and excitatory interneurons, respectively), while during the stance phase facilitating extensor -motoneurons via excitatory interneurons, which also in part receive convergent group Ia afferent inputs (for details see text). For simplicity, spindle group II afferents have been omitted. Furthermore, interneurons mediating presynaptic inhibition of sensory afferents are indicated by lled circles denoted PS. Group IIIIV afferents are symbolized by black dotted arrowed lines and may have oligo- and polysynaptic, excitatory or inhibitory effects (for details see text). Abbreviations: PS, interneurons mediating presynaptic inhibition; RC, Renshaw cell.

Phase-related locomotor-related modulation. Presynaptic inhibition also varies phasically throughout the locomotor cycle [317]. Sensory-evoked modulation. Rhythmic modulation of afferent input during natural locomotion also modulates presynaptic inhibition [317]. Supraspinal modulation. Signals descending from supraspinal sources may contribute to the phasic modulation of presynaptic inhibition [317]. Among the rhythmically active supraspinal neurons are brainstem (reticulo-, rubro-, vestibulospinal), cerebellar and cerebro-cortical cells [12].

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The descending tracts have effects not only on - and -motoneurons, but also on spinal interneurons, among which are those mediating presynaptic inhibition [154,164]. In humans, voluntary ankle movements are associated with changes in presynaptic inhibition [155]. Transcranial magnetic stimulation of the motor cortex differentially modulates presynaptic inhibition of group Ia afferents in human lower limb (depression) and arm (increase) [254]. In monkeys, sensory afferent terminals receive presynaptic inhibition from descending tracts (e.g., pyramidal tract), but not vice versa, which might help preserve the quality of descending motor commands during centrally initiated movements [161]. Note that it is usually the compound effect of all these modulations that determine the pattern of presynaptic control of afferent sensory inputs, this compound action mostly not being recorded, however [317]. 5.3. Reciprocal inhibition in action The strength of disynaptic reciprocal inhibition between antagonist -motoneuron pools depends on the motor task. This has been studied in humans and animals, using several motor paradigms, including locomotion and voluntary movements [66,153,154,261,272,329]. Here emphasis is put on changes of reciprocal inhibition during locomotion. During locomotion, reciprocal Ia inhibitory interneurons are driven by the locomotor CPG and their group Ia afferent inputs during the times when their muscle is active [317]. In walking decerebrate cat preparations, Ia inhibitory interneurons with group Ia input mainly from quadriceps re maximally during the stance phase [95]. During ctive locomotion in the cat, motoneurons and reciprocal Ia inhibitory interneurons receiving the same group Ia afferent input are active concurrently. Since the pharmacological blockade of the latters output synapses by strychnine does not interrupt the locomotor rhythm, however, they do not belong to the locomotor CPG [298]. Reciprocal Ia inhibition is also operative during ctive scratching [39]. In humans, reciprocal inhibition between ankle antagonist muscles decreases from quiet stance via walking to running, with locomotor speed being the major determinant [184]. Moreover, in line with the above cat data, disynaptic reciprocal Ia inhibition is rhythmically modulated during walking and bicycling, exerting small effects on the muscles being active in a phase [208,272,288,306]. The present view is that, during voluntary movement, the disynaptic Ia inhibition of the agonist muscles is decreased to facilitate their action, while the disynaptic Ia inhibition of the antagonist muscles is increased to ensure their silence and suppress stretch reex activity resulting from their stretch [272]. Part of the rhythmic modulation of reciprocal inhibition during locomotion may derive from supraspinal sources, as is the case for interneurons mediating presynaptic inhibition (Section 5.2). For example, the vestibulospinal tract monosynaptically excites extensor motoneurons and reciprocal Ia inhibitory interneurons projecting to antagonists [153,154]. In decerebrate

cats walking on a treadmill, a large subset of vestibulospinal neurons modulate their discharge rhythmically around a substantial mean rate, which consequently contributes a tonic background to postural support [277]. Thus, these neurons contribute to the extensor activity in an appropriate phase-dependent way. The rhythmicity of vestibulospinal neuron discharge originates, to a large extent, from the cerebellum [12]. Finally, part of the modulation of reciprocal inhibition during locomotion may also be due to modulation of presynaptic inhibition (Section 5.2) of group Ia terminals on reciprocal Ia inhibitory interneurons or, possibly, of terminals of reciprocal Ia inhibitory interneurons on -motoneurons [92]. The role of reciprocal inhibition in the co-contraction of antagonists to stabilize a joint is somewhat controversial. While some have argued that reciprocal inhibition is reduced during co-contraction [66,154], there is also some evidence to indicate that it should play an important role in increasing joint stiffness [268]. In summary, it has been shown that Ia interneurons mediate inhibition of antagonists not only during muscle stretches (Section 4.2), but also during centrally induced ctive locomotion, movements commanded by several descending systems including the corticospinal tract, crossed extensor reexes, and postural reexes initiated from the vestibular system [165]. They also contribute to the coordination of left and right hindlimb movements by mediating part of the crossed inhibition from reticuloand vestibulospinal tracts [167]. This multi-functionality is a characteristic of other spinal interneurons and requires a massive convergence of various inputs, which makes their workings so difcult to understand. 5.4. Recurrent inhibition in action The strength of recurrent inhibition depends on the motor task. This has been studied in humans and animals, using several motor paradigms, including voluntary movements [154,178,387,391]. Emphasis is here put on cat locomotion. 5.4.1. Recurrent inhibition in cat ctive locomotion Since the main excitatory input to Renshaw cells derives from -motoneurons, their discharge should be modulated rhythmically during locomotion and transfer this modulation to follower neurons they inhibit. In cat ctive locomotion, Renshaw cell discharge is modulated in phase with activity of their main input-giving -motoneurons, that is, most of them are active during either exion or extension when their predominant excitatory motoneuron pool is active [249]. Pharmacologically blocking recurrent inhibition does not disrupt the locomotor rhythm, indicating that Renshaw cells are no integral part of the locomotor CPG [274,298]. Under natural conditions, Renshaw cells may receive rhythmic modulating signals also from descending tracts [18,178,387,391], as is the case for interneurons mediating presynaptic inhibition (Section 5.2) and reciprocal Ia inhibitory interneurons (Section 5.3).

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5.4.2. Recurrent inhibition of reciprocal inhibition in cat ctive locomotion Since Renshaw cells inhibit related reciprocal Ia inhibitory interneurons (Fig. 3), the formers rhythmic discharge modulation might be reected in the latters discharge. In fact, in ctively locomoting cats, when extensor Renshaw cells increase their rate at the end of the extension phase, most of the quadriceps-related reciprocal Ia inhibitory interneurons decrease their discharge rate [298]. More generally, it has been proposed that the recurrent inhibition of reciprocal Ia inhibitory interneurons may serve to reduce reciprocal inhibition if the contraction forces of antagonist muscles are to be nely balanced, for example during alternating or ne exploratory movements, or if co-contraction of antagonist muscles is required [154,329]. As noted above (Section 5.3), the role of reciprocal inhibition in co-contraction of antagonists to stabilize a joint is somewhat controversial, however. 5.5. Compensation for muscle properties and joint nonlinearities During movement, a number of problems arise from the properties of musculo-skeletal systems, which the CNS has to take care of and may do so by using proprioceptive feedback. One set of problems relates to muscle properties, such as nonlinearities (Section 5.5.1), forcelengthvelocity relationships (Section 5.5.2) and muscle fatigue (Section 7), the other to muscle actions on joints. 5.5.1. Linearization of muscle stiffness When in a decerebrate cat an active soleus muscle is extended by a ramp-and-hold stretch, force rst increases steeply, due to the muscles intrinsic stiffness, which is commonly attributed to elasticity of existing acto-myosin crossbridges. This elasticity has only a short range of operation, which when exceeded by continuing stretch causes the muscle to yield. When the muscle is shortening using the same ramp-and-hold stretch but of negative sign, the fall in force is more dramatic than the rise in the former case, in particular due to the lack of yield. With an operating reex loop, both force responses become enhanced and, more importantly, more symmetrical to each other. This linearization is due to asymmetric changes in muscle activation by the reex. The activation induced by stretch is much larger than the de-activation induced by release (as measured by electromyographic activity), implying that the stretch reex contributes most to muscle mechanical responses during lengthening (eccentric) contractions [269]. Based on results such as those described above, Houk [147] discarded length-servo hypotheses such as Mertons (Section 5.1.3) and suggested that, rather than regulating muscle length or muscle force as individual variables, the stretch reex serves to regulate stiffness as a compound variable. In physics, stiffness of an elastic structure (e.g., a spring) is dened as the ratio of force change over length change. Length would be signaled by muscle spindle afferents and positively fed back to -motoneurons, while force would be signaled by Golgi tendon organs and be fed back negatively to -motoneurons (see Section 5.6). The

combined action of both autogenetic feedback systems would provide for stiffness regulation. The concept was then modied because it turned out that, in the decerebrate cat, the sensory receptors primarily responsible for the reexive yield-compensation during active muscle lengthening (eccentric contraction) are most likely the muscle spindles, in particular their group Ia afferents, which have just the right nonlinear dynamic stretchresponse properties to predict the impending decline in muscle force and preempt it by their reex action [149]. An important role for stiffness regulation during eccentric contractions of calf muscles was established by re-innervation experiments. In locomoting cats, eccentric contractions of the ankle extensors during the stance phase do not usually occur while walking on level ground or up a ramp, but while walking down a ramp. Cats whose triceps surae muscles in one hindlimb had been denervated and allowed to self-reinnervate (re-establishing motor, but not sensory muscle innervation) walked almost normally on level ground and up a ramp, but showed severe decits while walking down a ramp when the triceps surae muscles normally undergo active lengthening. The ankle joint yielded strongly suggesting an important role for the local stretch reex during the stance phase in downhill walking [1]. 5.5.2. Coping with muscle forcelengthvelocity relationships Asymmetric muscle behavior during concentric versus eccentric contractions has other consequences that must be taken into account by the CNS. These consequences arise from the well-known forcelength and forcevelocity relationships [279]. For example, when a load is to be lifted or lowered at the same velocity, the neural excitation of the acting muscle(s) should be different. If it were the same, the eccentric (lengthening) contraction would be more powerful than the concentric (shortening) contraction. Thus, less excitation is required for the eccentric contraction. In order to reduce the number of active motor units and their discharge rates, the reex effects of the stretch-evoked sensory discharge (supported by fusimotor co-activation of spindles) should then be tuned down, a prime candidate being presynaptic inhibition (Section 5.2). This appears to be the case for voluntary soleus muscle contraction against a load [311]. 5.5.3. Compensation for joint lever-arm variations Another problem of musculo-skeletal interactions derives from non-unique joint angle-torque relationships. Consider the following experiment. The human elbow joint is consecutively set at different angles covering the range of movement. At each angle, the exor elbow muscles are activated in such a way that the average electromyographic activity is kept at the same level. The muscles moment arm (mechanical advantage) changes from small to large to small when the elbow is extended from its most exed through an intermediate to a fully extended joint angle. This joint-angle dependence of moment arms should co-determine the torques produced. In fact, with constant muscle activation as measured by electromyographic activity, the

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measured torques peak at an intermediate angle and decline bilaterally towards smaller and greater angles [139]. This nonuniqueness of the torqueangle relationship, which could be a problem for central controllers, could be remedied by the stretch reex, which could recruit stronger muscle activation (and additional torque) with increasing joint angle and muscle length. The torque would then be a uniformly increasing function of joint angle. Thus, the stretch reex could automatically compensate for lever-arm variations with joint angle [140]. In fact, with constant descending motor commands, human elbow torqueangle relationships show a monotonic, slightly convex shape (convex to the angle axis), with the exor electromyographic activity increasing with elbow extension due to stretch reex action [23]. It has been suggested that the convexity could in part be due to the nonlinear (saturating) inputoutput relationship of recurrent inhibition [389]. 5.5.4. In search of a role for Golgi tendon organs From the results described above, it appears as if muscle spindles and their excitatory reex connections to homonymous -motoneurons could almost single-handedly cope with some nonlinearities of the musculo-skeletal system and thus also provide for stiffness regulation. Why then are there Golgi tendon organs, presumed force receptors? Indeed, . . . it is still not clear why both spindles (length detectors) and tendon organs (force detectors) are necessary ([356], p. 5). This question prompts an examination of their reex effects. 5.6. Spinal actions of group Ib afferents from Golgi tendon organs Over the years, the spinal reex effects exerted by group Ib afferents from Golgi tendon organs have turned out to be much more complex than originally envisaged. These effects are statedependent, that is, dependent on the context and task of motor acts. This task dependence is reected in different group Ib reex effects during quiescent states on the one hand versus upright stance and the locomotor stance phase on the other hand. Early studies in anesthetized, reduced preparations showed that group Ib afferents from extensor Golgi tendon organs exert di- or trisynaptic inhibition on extensor -motoneurons (called autogenetic inhibition), as well as the functional complement, namely di- or trisynaptic excitation on exor -motoneurons (see Fig. 4). The inverse pattern from exor group Ib afferents is also seen but is weaker. This pattern involves, respectively, inhibitory and excitatory Ib interneurons [154,163,164,329]. In addition to -motoneurons, the following neurons are affected by Ib interneurons [163,164,329]: -Motoneurons; Ib interneurons (mutual inhibition); Group II interneurons; Cells of origin of the ventral spino-cerebellar tract (VSCT cells); Cells of origin of the dorsal spino-cerebellar tract in Clarkes column (only by inhibitory Ib interneurons [164]; there is also a less common direct excitatory action of group Ib afferents on

dorsal spinocerebellar tract neurons; R.E. Poppele, personal communication); Primary sensory afferents, so that Ib interneurons can also act as, probably GABAergic, neurons exerting presynaptic inhibition (Section 5.2). If reex actions from group Ib afferents are to change depending on condition and motor task, the involved interneurons must be amenable to modulating inuences. In fact, Ib interneurons receive a tantalizing variety of convergent inputs from sensory afferents and descending tracts [154,163,164,329]. Particularly intriguing is the convergence of spindle Ia and tendon organ Ib afferents on subsets of lumbar interneurons. The afferents can have co-excitatory, co-inhibitory or mixed effects on the interneurons. Group Ia and Ib afferents are simultaneously active during lengthening contractions of muscles, which could thus be nely controlled by Ib effects related to both muscle force and length, or some derivative thereof. Interneurons receiving such convergent IaIb inputs are not only active during lengthening contractions, but also during other contractions, in which fusimotor activation excites Ia afferents and thereby indirectly Ib interneurons [163,164,329]. Widespread convergence of stretch-evoked and contraction-evoked sensory inputs also occurs in dorsal spinocerebellar tract cells (R.E. Poppele, personal communication). The IaIb convergence might suggest that the CNS does not separately control muscle length and muscle force but some more global variable (see below). While in quiescent reduced preparations Ib inhibitory actions most strongly affect extensor -motoneurons, and the excitatory action is most pronounced on exor -motoneurons, the reverse effects, though weaker, are also observed at times and attest to the existence of alternative reex pathways from group Ib afferents, which may be used differentially depending on motor task [154,163,164,329]. In particular, during upright stance and the stance phase of locomotion, group Ib afferents from extensor muscles exert strong excitatory actions on extensor -motoneurons (see Fig. 4; for distribution, see Section 9.4.6). We shall discuss this role in a wider functional context, in conjunction with other sensory systems. 5.7. Sensory force feedback during the stance phase During quiet upright stance and in the stance phase of the step cycle, the support of body weight against gravity is of paramount importance and in part implicates sensory feedback. 5.7.1. Contributions of sensory receptors to force feedback It is important to distinguish between two roles of afferent feedback during stance, one related to the generation of average background activity in extensors, and another related to amplitude modulations of the background activity in response to small perturbations, these two roles possibly being executed by at least partially different mechanisms [242244]. The sensory receptors responsible for the enhancement of extensor activity are still somewhat uncertain. Their signals may be related to different biomechanical parameters. In particular, while all potential receptors would be expected to signal load,

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they may do so in different ways. Thus, the following distinction of load receptors has been suggested [81]: Main load receptors: True load receptors: Golgi tendon organs in the ankle extensors of cats and humans. Body support receptors: Cutaneous afferents from the foot sole. Accessory load receptors: Neuromuscular receptors: Muscle spindle afferents from the ankle extensors. Joint receptor afferents from Rufni endings and Pacinian corpuscles. Muscle afferents and cutaneous afferents from the foot sole have been shown to contribute their share to extensor excitation during stance [73,78,81,248,317,382,409]. In the following, we will concentrate on contributions from Golgi tendon organs and muscle spindle afferents. 5.7.2. Golgi tendon organs During locomotion, the reex actions of group Ib afferents from Golgi tendon organs are re-organized from their state during rest. The classic, autogenetic, di- or trisynaptic inhibition from extensor Ib afferents onto homonymous and synergistic motoneurons is reduced or abolished during locomotion. Instead, extensor group Ib afferents activate ipsilateral extensor -motoneurons and inhibit exor -motoneurons, these effects being modulated in size in different locomotor phases [154,317]. Group Ib afferents from Golgi tendon organs also have access to the locomotor CPG, most probably exciting the extensor half-center and inhibiting the exor half-center [61,74,81,283,287,317]. Thus, extensor Ib afferents contribute to positive force feedback that helps regulate extensor force depending on the loading conditions of the whole limb. 5.7.3. Muscle spindle group Ia afferents According to the servo-assistance hypothesis (Section 5.1.4), extensor muscle spindle group Ia afferents with their monosynaptic -motoneuron connections look like the prime candidates for supporting the stance phase during walking. In fact, during the stance phase of cat locomotion, muscle spindle afferent discharge increases [299,301]. The quantitative signicance of group Ia afferent feedback has remained uncertain, however [73,78,282]. On the one hand, in humans, the synaptic transmission from group Ia afferents to -motoneurons and the H-reex are reduced from rest conditions through standing to walking, which presumably results from increased presynaptic inhibition (Section 5.2) and other factors [35,177,266,351,410]. Also, patients suffering from large-diameter sensory neuropathy and exhibiting an absence of H-reexes and tendon reexes show almost normal quiet stance and gait [244] (but see ref. [203]). Therefore, under normal quiet stance and walking conditions, the quantitative signicance of group Ia afferent feedback would appear to be rather low [78].

On the other hand, several ndings in cats and humans have suggested a substantial role of group Ia afferent feedback [1,336,404]. In faster forms of human locomotion (running and sprinting), during which larger -motoneurons are recruited, monosynaptic Ia reexes appear to signicantly contribute to triceps surae activation during the stance phase of the leg touching the ground [45,71]. A role for proprioceptive feedback in the ne adaptive control of extensor muscle activation is suggested by recent experiments in humans. Stretch reexes contribute signicantly, during the stance phase, to the amplitude modulation of soleus muscle activity in response to slow, small-amplitude ankle angle changes, which might occur naturally on even or slightly uneven ground. In this reex activity, responses from both group Ia and II muscle spindle afferents play the largest role, while load receptors, and cutaneous and muscle proprioceptive afferents from the foot, are of less or no signicance. Group Ib afferents might contribute to the unloading reex in extensors, however [242,244]. Contributions to extensor muscle activity may also come from oligosynaptic group Ia afferent reex pathways to motoneurons in parallel to the monosynaptic connections [39,50,382]. In cats, these partially disynaptic excitatory Ia pathways are in part shared with group Ib afferents from Golgi tendon organs [9,248] and appear to be mediated by excitatory interneurones in lumbar segment L7 [10]. 5.7.4. Muscle spindle group II afferents What about group II muscle spindle afferents? Besides their weak monosynaptic excitation of homonymous -motoneurons (Section 4.1.2), group II afferents exert a bewildering variety of reex effects on various -motoneuron pools, which depend strongly on the state of the CNS. Moreover, there are alternative excitatory and inhibitory pathways to each -motoneuron pool, which are under separate supraspinal control. The minimal central linkage in both the excitatory and inhibitory pathways is disynaptic. Group II afferents are subject to presynaptic inhibition, with the responsible interneurons receiving various sensory afferent and descending inputs. Sub-groups of these interneurons usually receive various combinations of other segmental afferent inputs (group Ia and Ib; mechanosensitive and nociceptive cutaneous; joint; and groups IIIIV muscle afferents) and descending inputs (cortico-, rubro-, reticulo- and vestibulospinal tracts; monoaminergic descending tracts). Sub-groups of group II interneurons mutually inhibit each other [164,329]. The contribution of muscle spindle group II afferents to stance support is not quite clear at the moment. In the cat, they do not appear to be of much signicance. Their discharge is low and poorly modulated during locomotion, and their effects on extensor -motoneurons are negligible [78,248]. By contrast, in humans, group II muscle spindle afferents from extensors could play a more important role [126,343]. 5.7.5. Intermediate summary Hence, during the locomotory stance phase, both extensor group Ia and group Ib afferents exert excitatory reex effects onto extensor -motoneurons. This common action is

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not compatible with the original stiffness regulation hypothesis (Section 5.5.1), in which group Ia afferents, supposed to signal muscle length, have excitatory autogenetic effects on extensor -motoneurons, and group Ib afferents, supposed to signal muscle force, should have inhibitory autogenetic effects on extensor -motoneurons [164]. The open-loop gain of the force-feedback system has been estimated to lie in a range of 0.20.5, which is sufcient to produce a signicant contribution to extensor -motoneuron activity [282]. 5.8. Interactions between sensory feedback and pattern generators Sensory afferents are of special signicance in switching between different locomotor phases. In particular, afferent signals related to joint-angles, loads carried by the limbs and cutaneous feedback play varying roles [282,317]. These effects are summarized only briey here. 5.8.1. Stance-to-swing transition The stance-to-swing transition and exor muscle activation are promoted by two groups of afferent signals, hip-positionrelated and load-related signals [81,205,248,282]. When, during cat walking, the hip angle reaches a threshold extension angle, the exion phase is promoted. This effect is likely to result from stretch of hip exor muscles (e.g., iliopsoas) and certain ankle exors (e.g., extensor digitorum longus and tibialis anterior) at the end of the stance phase [205]. Of particular importance for this muscle length-dependent effect may be a group of interneurons identied in the cats mid-lumbar segments, which receive monosynaptic excitatory input from group II muscle spindle (and other) afferents from hip muscles, and have been hypothesized to be involved in the phase switch from extension to exion [164]. Another system, which may be involved in switching from extension to exion, is reciprocal inhibition. During human walking, the ankle exors (tibialis anterior and extensor digitorum longus) are stretched in the late stance phase, i.e., between heel off and toe off ground. Their muscle spindle Ia afferents should be excited during this period and help activate their own (agonist) -motoneurons as well as inhibit the antagonist soleus -motoneurons [44]. The relative importance of load signals and hip-extension signals for intitiation of the stance-to-swing transition is difcult to determine in physiological experiments. A recent computer simulation study suggests that a force-related signal at the end of the stance phase is crucial for regulating the stance-to-phase transition, while a hip-extension signal alone would not guarantee normal locomotion [85,285]. In analogy to the stance-to-swing transition, sensory signals related to hip position are also important in regulating the swingto-stance transition in locomotion of decerebrate cats [251,317]. 5.8.2. Drawing inferences and making choices It appears from the above that the timing of phase transitions during locomotion depends on combinations of sensory signals. This implies that there must be central neuronal networks that draw inferences from sensory inputs and make choices using

rules as follows. The general rule is: IF sensory state 1 AND sensory state 2, THEN perform this particular action. For example, for slow forward gait of a cat: IF the extensor force is low AND the hip is extended AND the contralateral leg is loaded, THEN ex the ipsilateral leg. Or, for backward gait: IF the extensor force is low AND the hip is exed AND the contralateral leg is loaded, THEN ex the ankle and knee and extend the hip [299,300]. The description in terms of such rules is likely to be heuristic and does not say anything about how the nervous system really works when solving motor problems [299]. It suggests the existence of pattern recognition networks [387], based on the convergence of several sensory afferent inputs onto interneurons used to classify sensory inow [361]. As discussed above, such convergence is ample in the spinal cord. In particular, muscle spindle afferent and Golgi tendon organ afferent inputs converge on common interneurons and muscle spindle group Ia and II converge on other common interneurons [164]. 6. Stabilization of motor output In the mathematical literature in general and in biological motor control in particular, stability is not dened unanimously. Nor does it represent a value per se in the sense that the nervous system should immediately act to oppose any small perturbation at the cost of maneuverability [138]. Under some conditions, however, some variables must be stabilized against internal and external perturbations, with mechanisms to compensate for these perturbations. For example, external perturbations in foot placement and load transfer arise from uneven and insecure ground, and internal perturbations from uctuations in motor activities due to neural noise and muscle fatigue (Section 7). 6.1. Positive force feedback: risk of instability Some hazards to stability may arise from inherent properties of neuromuscular feedback systems. Even negative feedback control systems may become unstable under particular conditions, namely signal-transmission delays and phase lags summing up to 180 and high (>1) open-loop gain at particular frequencies, which would lead to oscillations of increasing amplitudes. Even more precarious should be the situation in systems whose feedback is positive right away. It is therefore important to know how the nervous system deals with positive force feedback used in stance. As a heuristic example providing insights into potentially stabilizing mechanisms, let us consider a model. Prochazka et al. [302] developed a nonlinear model of the cats hindlimb segmental reex system in the stance phase of walking. The behavior of muscle spindle group Ia afferents and tendon organ group Ib afferents were modelled by linear transfer functions or, alternatively, by two variants of a nonlinear spindle group Ia model. Positive feedback via the -fusimotor pathway was included. Separate delays were assumed for the spindle group Ia, tendon organ group Ib, and -fusimotor reex pathways. The group Ia delay was assumed to be small (e.g., 1020 ms). The posi-

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tive group Ib feedback had a delay or rise time of 3040 ms, but delays of up to 100 ms were tested. Loading was provided as two-step changes in force. The second load was added to explore the behavior of the loop after stabilization to the rst load. In this model, positive force feedback provided for effective load compensation at high enough gains. The associated risk of instability was reduced by (i) automatic gain control of the muscle length-tension characteristics (length-dependent muscle stiffness, operative when muscle shortens), (ii) long delays in the force-feedback loop, (iii) negative muscle-length feedback via muscle spindles at shorter delays, (iv) positive feedback via the -skeleto-fusimotor feedback [302]. These results may appear surprising, but nd support in other investigations showing that the very presence of multiple meshed feedback loops with different properties (e.g., different delays) may increase stability [276]. Also, in a model including muscle spindle feedback, reciprocal Ia inhibition and recurrent inhibition, the latter was suggested to suppress oscillations [354]. In another model using experimentally measured frequency characteristics of the motor axon-Renshaw cell and the motor unit-spindle afferent subsystems, it turned out that Renshaw cells have frequency characteristics well suited to contribute to the stabilization of the reex loop, at low gains of recurrent inhibition [395]. These last examples unveil the conspicuous absence of recurrent inhibition in the model of Prochazka et al. [302], although the short latency of recurrent inhibition would seem just right to contribute to stability. 6.2. Motor output uctuations, muscle proprioceptors and recurrent inhibition Even in the absence of external perturbations, the seemingly simple task of maintaining a constant position or force cannot be performed adequately without feedback from muscle afferents, and the absence of proprioceptive feedback leads to tremor and/or shifts in position or force. Proprioceptors may thus contribute to the stabilization of self-generated motor output [140]. Harking back to Sherringtons concept of proprioception (footnote 1), Evarts [94] hypothesized that: (i) Segmental reex actions by proprioceptors are most efcient with smallamplitude inputs; (ii) such reexes deal with small internal disturbances arising from irregular motor unit activity and creating errors of movement or tremor around a maintained mean (or slowly changing quasi-isometric) position. One may add that external disturbances are of signicance, too, but potentially of secondary importance [140]. In a similar vein, from their work on jaw movements in monkeys, Goodwin et al. [119] suggested that muscle spindle afferents play a signicant role in reducing errors of muscle length produced by uctuating levels of motor discharge as well as external loads (p. 83). 6.2.1. Physiological tremor and muscle proprioceptors Tremor occurs in a variety of forms, from physiological to pathological types [352]. Even physiological tremor expresses itself in different forms, which result from interactions of several different mechanisms, with different predominance of one or the other depending on conditions [56,246,387,391].

One basic mechanism of physiological tremor (at a frequency of about 612 Hz) resides in the patterns of motor unit recruitment and discharge during steady contractions [4,55,246,387]. At each level of constant contraction force, the motor units recruited last discharge at fairly low, semi-regular rates and produce the largest twitch forces, leading to force oscillations whose superpositions generate a whole-muscle force uctuation waxing and waning throughout the contraction. These intrinsic cell-based oscillations may be reinforced by the fact that, due to common inputs, the ring patterns of different motor units show a tendency towards synchronization on a short-term time scale [246,387], such that the degree of this synchronization in humans is correlated with the mean amplitude of tremor oscillations [76]. Such synchronized discharges may in turn show a rhythm [56,136], which may reect the rhythmicity of common inputs, resulting from: (a) rhythmically ring common presynaptic neurons, (b) rhythmic synchronization of rhythmically ring presynaptic neurons, and (c) the common rhythm of groups of presynaptic neurons with rhythmically modulated ring patterns (for references, see ref. [68]). For example, central oscillations of supraspinal origin may contribute their share [246,307]. One rhythmic common input to -motoneurons that, under certain circumstances, generates a temporally more widely dispersed synchronization originates from proprioceptors, thus constituting another mechanism. Since muscle spindles and Golgi tendon organs react to the unfused contractions of even individual motor units [29,30,387], their afferent discharge is modulated by internal length uctuations and force oscillations generated by synchronized unfused motor unit contractions. Especially group Ia afferents from primary spindle endings with their high dynamic sensitivity to small-amplitude length changes [151,171,239] and their monosynaptic connections to homonymous -motoneurons have long been implicated in promoting an oscillation in the stretch reex arc [56,212,246,387]. This would be in line with a modeling study indicating that the velocity sensitivity of group Ia afferents is too large to stabilize the stretch reex by just compensating for lags in the loop (Section 6.3.2) and thus produces a tendency towards oscillation [353]. In both cat soleus muscle and human exor pollicis longus muscle loaded by an inertial load, damping in the neuromuscular system is smaller at lower than higher oscillation amplitudes; this nonlinearity may thus contribute to physiological tremor, but also limit its amplitude [210,211]. The human digastric muscle lacking muscle spindles does not show tremor [80]. Very likely these various mechanisms act in parallel and interact with each other, one or the other predominating in various situations. In steady muscle contractions, the 612 Hz tremor component, which is associated with a tendency toward motor unit synchrony, appears to critically depend on group Ia muscle spindle feedback and is thus probably caused by rhythmic action in the stretch reex loop [56]. As mentioned above, central oscillations of supraspinal origin may also contribute their share to tremor. Again, however, during voluntary muscle actions of awake monkeys, such oscillations appear in muscle activity and presumed spindle group Ia afferent ring, which might implicate the stretch reex [16].

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During maintained muscle contractions, physiological tremor often slowly increases in amplitude and decreases in frequency, and also increases with stress. This enhanced tremor at a frequency of 68 Hz probably also involves the stretch reex [135,246]. In spasticity, clonus at a similar frequency of 68 Hz has long been assumed to be the expression of enhanced stretch reex activity, for example in spasticity. Finally, progressing muscle fatigue (Section 7) is associated with an increase in tremor, and this enhancement appears to be facilitated by muscle afferent input [64]. Little is known about the likely involvement of interneurons in physiological tremor, although many interneurons should discharge rhythmically in response to rhythmic sensory and descending inputs. Rather than being merely disadvantageous, physiological tremor may also have some benets. Small-amplitude oscillations may linearize muscle properties [353]. Larger-amplitude tremors may assist in fast alternating voluntary movements and their timing, and stretch reex oscillations may be used in repetitive movements such as running, hopping and, as mentioned above, paw shakes [246,387] (see also [138]. 6.2.2. Physiological tremor and recurrent inhibition Since recurrent self-inhibition of -motoneurons has been suggested to play a role in the regulation of -motoneuron discharge on a short-term time scale, it might as well have a role in physiological and, perhaps, pathological tremors [391]. The precise nature of this inuence is still unclear, and the available experimental evidence is controversial. Thus, some authors argue that Renshaw cells de-synchronize or de-correlate -motoneuron discharge [2,114,226] or otherwise reduce the tendency towards instability in the motor system and stretch reex loop [122,354,395]. Other authors suspect Renshaw cells of enhancing or generating tremor via effects on -motoneuron discharge [86,238]. A recent computer simulation study suggests that recurrent inhibition slightly enhances the tendency of motoneuron short-term synchronization [372]. 6.2.3. Intermittent motor control and muscle proprioceptors During slow voluntary nger and wrist movements in humans, pulsatile joint-angle changes recur at a mean rate of about 810 Hz. It has been proposed that these rhythms, rather than being neural noise, reect series of bipolar pulses in motor commands descending from supraspinal sources [132,172,380]. The high dynamic sensitivity of primary muscle spindle endings to small-amplitude length changes [151,171,239] and of Golgi tendon organs to individual motor unit contractions [29,163] renders these receptors optimally suited to signal small-amplitude movement irregularities [387]. Indeed, muscle spindle and Golgi tendon organ afferents react sensitively to the rhythmic pulsatile events occurring during nger movements [380]. It has been argued, however, that these rhythms are indendent of the stretch reex [381]. Nonetheless, the two rhythms are likely to interact with each other. Rapid primate limb movements often exhibit multi-peaked velocity proles, which have been interpreted by some as evidence for intermittent rather than continuous motor control processes [99,100] (see also [138]). These

discontinuities occur irregularly, however. Also, series of intermittent ballistic-like biphasic torque pulses generated by a neural feedforward predictor have been suggested to ensure upright human stance because ankle stiffness alone is not sufcient [138,204,219] (see also [259]). The precise role of proprioceptors in this intermittent motor control remains to be determined. Also, whether recurrent inhibition plays any signicant role is unknown. 6.3. Compensation for reex delays In any case, oscillations in the stretch reex loop [212] could go astray and lead to large-amplitude tremor, such as in muscle fatigue (Section 7) and clonus in spasticity. Since these oscillations are based on the sluggish muscle contraction dynamics and signal-transmission delays around the reex arc, such delays remain a problem to be kept in check. This could be done, in part, by counteracting the phase lags with phase leads. Indeed, the stretch reex has been shown to possess some phase advance mechanisms [241]. 6.3.1. Compensation of muscle-unit dynamics by -motoneuron discharge Muscles and their constituting muscle units are sluggish, albeit to varying extents depending on muscle-unit type. This property is expressed as pronounced low-pass characteristics, implying that the force amplitude modulation declines and the phase lag increases with increasing activation frequency above roughly 0.51 Hz [279]. For the nervous system using motor units, it might be advantageous to speed up muscle units for quicker action. This would require that the muscular low-pass properties be compensated for, at least partially, by some neural mechanism(s). Indeed, part of the compensation for muscular phase lags is provided by -motoneurons themselves. The required high-pass characteristics are borne out by the responses of -motoneurons to intracellular injections of currents of ramp shape or sinusoidal time course. When a cat -motoneuron is injected with a sinusoidal current superimposed on a suprathreshold steady bias current, the -motoneurons discharge is modulated sinusoidally, at least at lower modulation frequencies. The ratio of ring-rate modulation amplitude over current amplitude is about constant for low frequencies up to ca. 0.51 Hz and increases thereabove. Furthermore, ring-rate modulation shows a phase advance over the input-current modulation [17]. These dynamic -motoneuron properties can compensate for muscle sluggishness to some extent, but not completely. In any case, they certainly speed up the dynamic performance of the overall motor-unit system, with transmembrane current as input and force as output [17]. This implies that -motoneurons implement, to a degree, inverse models of their muscle units. 6.3.2. Phase advance by muscle spindle dynamics In a similar vein, phase lags due to muscle sluggishness and signal-transmission delays in the reex arc may be partially compensated for by high-pass characteristics of muscle spindle group Ia afferents [353]. Using a linear systems analysis

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approach to the cat stretch reex, Poppele and Terzuolo [296] showed the spindles to exhibit phase-lead characteristics complementary to the phase-lag dynamics of skeletal muscle so that the stretch reex characteristics were at below 10 Hz. In the human biceps brachii muscle, the phase advance contributed by group Ia afferents has been estimated to be roughly 90 at 10 Hz [241]. In addition to monosynaptic group Iamotoneuron connections, oligosynaptic such connections might also contribute to the phase advance. Furthermore, since group II spindle afferents [294] and Golgi tendon organ afferents [8] also exhibit phase advances of up to 90 at 10 Hz, their oligosynaptic reex connections to -motoneurons could contribute a share. Finally, interneuronal networks, such as presynaptic inhibition and recurrent inhibition, have been considered as potential generators of phase advances [241]. 6.3.3. Phase advance by recurrent inhibition? The potential mechanisms mentioned above are difcult to study experimentally, in particular in humans. Instead, modeling may provide some insights. The proposition that recurrent inhibition might further enhance the phase advance of -motoneurons [241] may not hold uniformly because the effects of recurrent inhibition might depend on recruitment level. This is suggested by model calculations that employed frequency responses of different -motoneuron types and Renshaw cells, derived from physiological data. At a low recruitment level with only S-type -motoneurons active, the intrinsic motoneuronal phase advance at around 10 Hz was reduced by recurrent inhibition, while the effects were more complicated at higher recruitment levels with also FR- and/or FF-type -motoneurons active [394,395]. A possibility to study the possible contribution of recurrent inhibition to the phase advance of motor output in humans along Matthews [241] approach might be to enhance its action by intravenous administration of l-acetylcarnitine [238,245,325]. 7. Compensation for muscle fatigue Muscle fatigue is a severe internal disturbance of the peripheral mechanical apparatus, which must be taken care of by the nervous system while generating posture and movement. Muscle fatigue becomes manifest as . . . any reduction in the force generating capacity of the total neuromuscular system regardless of the force required in any given situation ([27], p. 691). This decline involves processes at all levels of the motor pathway from the brain to skeletal muscle [90,91,111]. Processes in the CNS are subsumed under central fatigue, denoting a failure of the CNS to drive -motoneurons maximally. A component of central fatigue is supraspinal fatigue, . . . dened as an exerciseinduced decline in force caused by suboptimal output from the motor cortex ([366], p. 400). The mechanisms underlying the decline in maximal force capacity depend on the details of the task being performed. Critical task variables include the type and intensity of exercise, the type of load supported during the contraction, the muscle groups involved, and the specics of the task environment [228].

Nature has evolved a number of mechanisms for maintaining force output at the optimum achievable at any time. The rst line of defense against fatigue is the development of different types of motor units, with the S-type units being fairly fatigue-resistant and thus being predominantly recruited during long-lasting, low-force muscle contractions, such as those required for quiet upright stance [38]. In many motor acts, however, this is not possible because faster and more fatiguable motor units need to be recruited. Then, further mechanisms are required to at least mitigate the effects of fatigue. Study of these mechanisms not only reveals specics about muscle fatigue, but also provides insights into how the CNS optimizes the performance of its neuromuscular periphery [393]. We will here focus on spinal mechanisms. 7.1. Actions of the stretch reex Negative feedback control systems are well suited to compensate not only for external disturbances, but also for inherent deciencies of the system [148]. The stretch reex may thus be expected to considerably contribute to compensation for muscle fatigue. Indeed, based on various assumptions and two different methods, Kirsch and Rymer [187] estimated the open-loop gain in the compound force feedback system of the human elbowexor muscles to average between 1.27 and 4.61 (rst method) or 8.31 (second method) and concluded that these unexpectedly high loop gains may signicantly reduce the susceptibility of the overall neuro-muscular system to fatigue by 5689%. In human elbow extensor muscles, after fatigue, joint stiffness was signicantly decreased at higher torque levels, probably resulting from the reduced force-generating capacity of the muscle bers, while joint viscosity was increased. The static stretch reex gain decreased with fatigue, potentially due to changes in muscle spindle chain bers and bag2 bers. By contrast, at matched pre- and post-fatigue torque levels, the dynamic stretch reex gain increased, thus counteracting the fatigue-induced reduction of intrinsic joint stiffness and static stretch reex gain [411]. The stretch reex sensitivity may also be increased during precision tasks such as holding a position, during which the required contractions fatigue more rapidly than during isometric force-holding contractions [228]. 7.2. Muscular wisdom Results from a specic experimental paradigm in humans have led to the notion of muscular wisdom [111,233,393]. During prolonged maximal voluntary muscle contractions under isometric conditions, human motor units start ring at a high rate that subsequently adapts to lower rates over several tens of seconds. This discharge adaptation has been hypothesized to adjust the discharge intervals to the lengthening motor unit contractions during progressing fatigue and thus to optimize force output. Several different, albeit interacting, mechanisms might contribute to this adjustment: Intrinsic motoneuron properties; Diminishing descending motor commands;

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Diminishing facilitation from muscle spindle afferents; Reex effects from groups IIIIV muscle afferents that are increasingly excited by metabolites released by the fatiguing muscle bers [111,112,392,393] effecting: Inhibition or excitation of -motoneurons; Excitation of -motoneurons; Changes in autogenetic inhibition from Golgi tendon organs; Changes in recurrent inhibition via Renshaw cells; Changes in presynaptic inhibition. 7.2.1. -Motoneuron discharge adaptation Intrinsic -motoneuron properties may contribute to the late adaptation of discharge rate through a variety of potential mechanisms. Appropriately, late adaptation is more prevalent in F-type -motoneurons innervating easily fatiguable muscle bers than in S-type -motoneurons innervating fatigue-resistant bers. Also in F-type motor units, the initial high discharge rate promotes potentiation of the elicited twitches, thus transitorily counteracting and delaying force loss [393]. 7.2.2. Diminishing descending motor commands Voluntary -motoneuron activation declines with fatigue. For example, during isometric maximal voluntary contractions of the elbow exor muscles, transcranial magnetic stimulation (TMS) of the contralateral motor cortex evoked an additional small twitch-like increment in exion force, indicating that, despite the subjects maximal effort, motor cortex output was not maximal to drive the -motoneurons so as to produce maximal force. The exercise-induced increase of this TMS-evoked increment indicates supraspinal fatigue, which is linked to the exercising muscles. Supraspinal fatigue also constitutes a component of the fatigue developing during sub-maximal voluntary contractions. The underlying mechanisms are still unclear, one possibly involving feedback from fatigue-sensitive muscle afferents [111,347,366]. Recovery from central fatigue is faster than that from peripheral fatigue [347]. 7.2.3. Diminishing support from neuromodulatory systems? Changes in descending monoaminergic systems might also contribute to central fatigue. The discharge properties of -motoneurons may be altered drastically by a number of neuromodulators, including serotonin (5-HT), noradrenaline, glutamate, acetylcholine, thyroid-releasing hormone, adenosine, substance P, and other neuropeptides [143,275]. In particular, the monoamines serotonin and noradrenaline facilitate so-called persistent inward currents that are generated by voltage-sensitive calcium and sodium channels, which do not inactivate upon prolonged opening and may cause plateau potentials and, hence, maintained discharge. They also reduce postspike after hyperpolarization. -Motoneurons in fatigue-resistant S-type motor units exhibit a particularly strong tendency toward plateau potentials appropriate for their postural functions requiring sustained discharge. Thus, serotonin and noradrenaline reduce the ring threshold

and increase the inputoutput gain of -motoneurons by greatly enhancing the effect of ionotropic synaptic inputs [143]. The development of the persistent inward current with strong enough monoaminergic inputs may, however, obviate the initial and late phases of -motoneuron adaptation so that, in humans, motor unit rate adaptation may not contribute substantially to fatigue during sustained muscle contractions [275]. In addition to -motoneurons, spinal interneurons are also subject to neuromodulation by monoamines [319], which might alter the operation of certain reex pathways, such as those from group II afferents (Section 5.7.4). During normal motor behaviors, such as locomotion, monoaminergic signals descending from the brainstem (Section 5.1.6) may be assumed to be moderately strong, and very strong during ght or ight reactions [143]. In behaving cats, the activity of serotonergic neurons in the medullary raph e nuclei is positively correlated with the tonic level of motor activity (muscle tone) and often increases before rhythmic activities including locomotion. During prolonged treadmill locomotion leading to fatigue, serotoninergic neurons gradually reduce their initially elevated ring activity, and the ensuing dis-facilitation of -motoneurons may contribute to the development of central fatigue [102,162]. Whether similar changes occur in humans during prolonged fatiguing muscle contractions, remains to be studied in detail. 7.2.4. Diminishing facilitation from muscle spindle afferents In the course of fatiguing (sub-maximal) muscle contractions, human muscle spindle afferents reduced their mean discharge rate, possibly due to a reduction in fusimotor drive to the spindles. The ensuing disfacilitation of their homonymous and synergistic -motoneurons might contribute to the decline of their ring rate. Group II afferents from muscle spindles may add to these effects [393]. 7.2.5. Actions of chemosensitive group IIIIV muscle afferents on spinal neurons Muscle fatigue may in part be signaled to the CNS by small-diameter nerve bers of groups III (A) and IV (C), which may be activated by mechanical and chemical stimuli in the working muscle. These bers distribute signals to the brainstem [225] and thus inuence the cardio-vascular and respiratory systems, contributing to this part of body wisdom. In addition, however, they project to the spinal cord [292], where they exert actions on the motor system via a number of reex mechanisms. Here, as schematically illustrated in Fig. 4, they inuence the activities of many different types of neuron, including - and -motoneurons, various sorts of interneurons, and preganglionic sympathetic neurons [111,392,393]. The effects exerted are complex and not well understood. 7.2.6. Actions of chemosensitive group IIIIV muscle afferents on -motoneurons Activation of chemosensitive group IIIIV muscle afferents (by substances such as potassium chloride (KCl),

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bradykinin, serotonin, etc.) reexly inuences -motoneurons and -motoneurons via polysynaptic pathways. This complex inuence consists of changes in excitatory or inhibitory bias to -motoneurons as well as changes in their inputoutput gains, mediated by effects on intrinsic properties, such as input resistance and post-spike after-hyperpolarization [392]. In acute decerebrate cats, the effects of chemosensitive ankle-extensor group IIIIV muscle afferents on -motoneurons complied largely with the exor-reex pattern: excitation of ipsilateral exors, inhibition of ipsilateral extensors, activation of contralateral extensors. There were exceptions, however, indicating the possible existence of alternative reex pathways from chemosensitive group IIIIV muscle afferents to (ipsilateral) -motoneurons [188]. Intrinsic negative feedback is exerted by the post-spike afterhyperpolarization that transiently reduces the -motoneuron excitability. In acute decerebrate cats, activation of chemosensitive groups IIIIV muscle afferents by intra-arterially injecting algesic substances caused moderate to strong increases in -motoneuron synaptic noise (see also [188]), reduced motoneuron input resistance, and decreased afterhyperpolarization amplitude and area (time integral of afterhyperpolarization) [392]. In humans, fatigue in a muscle has been hypothetized to exert an inhibitory reex effect on homonymous -motoneurons, presumably originating from activation of fatigue-sensitive group III and IV afferents [112]. In human elbow muscles, the activity of fatigue-sensitive group IIIIV muscle afferents from homonymous and antagonist muscles depressed extensor motoneurons but facilitated exor -motoneurons consistent with the above exion-reex pattern [234]. This inhibition would also be consistent with the reduction in static stretch reex gain mentioned above [411]. 7.2.7. Actions of chemosensitive group IIIIV muscle afferent bers on -motoneurons Chemosensitive group IIIIV muscle afferents also exert indirect actions on -motoneurons via the -loop, involving -motoneurons, muscle spindles and their connections to -motoneurons. In cats, in contrast to -motoneurons, motoneurons were almost uniformly excited by intra-arterially injected algesic substances (potassium chloride, bradykinin, histamine, serotonin and lactic acid), irrespective of whether the -motoneurons innervated muscle spindles in exor or extensor muscles [170,328]. In a series of studies on -chloralose-anesthetized cats, the effects of injecting neurochemicals (potassium chloride, lactic acid, arachidonic acid, bradykinin, serotonin, hypertonic saline) into the calf muscles were investigated on muscle spindle afferent discharge altered via fusimotor reexes. These studies showed that (i) spinal reex actions of chemosensitive groups IIIIV muscle afferents were different on dynamic and static -motoneurons, with a predominant activation of static motoneurons, and (ii) these changes in fusimotor output altered the mean discharge rate and stretch sensitivity of group Ia and group II muscle spindle afferents [392].

7.2.8. Actions on Ib inhibitory interneurons Effects on non-reciprocal group I inhibition exerted by chemically activated group IIIIV muscle afferents have been studied in animal and human experiments. Results in acute cat preparations varied from those in normal humans. The contrasting results of the animal and human experiments were probably due to the different experimental paradigms, including differences in wakefulness, integrity of the CNS, and the site of group IIIIV activation relative to the tested group Ib pathway [392]. Repeated eccentric contractions (e.g., in calf muscles during prolonged down-hill walking or running) may lead to muscle fatigue, muscle damage, intramuscular inammation and delayed-onset muscle soreness. While active muscle force declines, passive force increases, probably as a result of local contractures subsequent to increases in intra-ber calcium concentration. The changes in muscle forces are monitored by Golgi tendon organs, which in turn may have central consequences on motor control, the details needing further elucidation [125]. 7.2.9. Actions on recurrent inhibition In humans, recurrent inhibition has been suggested to become stronger during sustained maximal voluntary contraction [195] and upon chemical activation of groups IIIIV muscle afferents [315], but to decrease during sustained fatiguing sub-maximal muscle contraction [218]. In cats, after fatiguing activation of the gastrocnemiussoleus muscles, recurrent inhibition of homonymous/synergistic -motoneurons was reduced, while presynaptic inhibition was increased [175]. These effects probably result from central actions of groups IIIIV muscle afferents activated by intramuscular interstitial accumulation of metabolites and/or inammatory substances. Such substances are indeed able to modulate the discharge characteristics of Renshaw cells as demonstrated by Windhorst et al. [397]. The background activity (bias) of Renshaw cells was predominantly reduced during activation of chemosensitive groups IIIIV muscle afferents, which would entail a disinhibition of -motoneurons. In addition, the inputoutput gain (Renshaw discharge over motor axon excitation) decreased, entailing an increase in -motoneuron inputoutput gain [392]. 7.2.10. Actions on interneurons mediating presynaptic inhibition The interneurons mediating presynaptic inhibition are controlled and modulated by a variety of spinally descending tracts and segmental afferents including groups IIIIV muscle afferents (Section 5.2). A recent study [314] in man showed that muscle nociceptive activity evoked by injection of levo-ascorbic acid into a foot muscle depressed, in soleus -motoneurons, the excitation resulting from large-diameter group Ia bers from muscle spindles. The authors concluded that the evoked nociceptive activity facilitated interneurons intercalated in pathways responsible for presynaptic inhibition of soleus Ia bers. An enhancement of presynaptic inhibition has also been suggested to occur during muscle fatigue in humans [15], during muscle fatigue in rats, where it was ascribed to the activation of capsaicin-sensitive groups IIIIV afferents [289], and after fatiguing activation of the gastrocnemiussoleus muscles

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in cats [175]. The increase in presynaptic inhibition during activation of chemosensitive groups IIIIV muscle afferents reduces the efcacy of proprioceptive inputs from group Ia afferents from muscle spindles and group Ib afferents from Golgi tendon organs. This effect thus reduces the gain of signal transmission from these afferents, and shrinks the input range of excitatory Ia signals to -motoneurons. This restriction would reduce the motor resolution in response to any input, which might lead to coarser control and reduced accuracy of motor output [392]. 8. Summary and comments Decades of experimental work on spinal sensory-motor systems have led to some general operational ideas or principles [164,165], which can also be considered as guidelines for future research. Flexibility. Functionally, spinal networks are anything but xed and prewired so as to yield, for instance, stereotypic reexes. Thus, reexes can be adjusted to the type, intensity and site of action of stimuli and their context [153,154,165]. Fractionation. Spinal neurons are divided into populations and sub-populations according to differentiated inputoutput patterns and functional actions. This applies to: Descending tracts (Section 5.1.6); Sensory afferents; Motoneurons. Skeletal motoneurons are, rstly, divided into - and -motoneurons (footnote 2) and, secondly, innervate different types of muscle units, which are used differentially in different motor acts; -motoneurons are commonly divided into dynamic and static varieties (Sections 5.1.4 and 5.1.5); Interneurons are divided into broad populations based on their predominant inputs and outputs, e.g., reciprocal Ia inhibitory interneurons (Section 4.2), Renshaw cells (Section 4.3), group Ib interneurons (Section 5.6), group II interneurons (Sections 4.1.2 and 5.7.4), interneurons mediating presynaptic inhibition (Section 5.2). Further sub-divisions within a population may result from differentiated distributions of inputs and outputs. For example, in the group Ib pathways, only inhibitory interneurons appear to affect both -motoneurons and dorsal spinocerebellar tract cells [164] (Section 5.6). Interactions between various neuronal populations [165]. For example, Renshaw cells inhibit reciprocal Ia inhibitory interneurons; inhibitory Ib interneurons inhibit dorsal spinocerebellar tract cells, etc. Multi-functionality. Neuronal networks and individual neurons may serve different purposes [154,165,387]. Even skeletal muscles do, and so do sensory afferent systems. It comes as no surprise, then, that central neurons do so as well. For example, reciprocal Ia inhibitory interneurons may exert antagonist inhibition during reexes, ctive locomotion, and/or descending motor commands (Sections 4.2 and 5.3). Neuromodulation. The operation of spinal neuronal systems is differentially modulated by descending monoaminergic systems (Section 7.2.3).

Alternative reex pathways may be activated depending on state and motor task, as exemplied by the actions of group Ib afferents during rest versus stance (Section 5.6). Also, in decererate preparations, reexes evoked by group Ib afferents may completely disappear [164]. These are merely two examples of how spinal networks may be reorganized depending on state and task [153,154,165]. Such changes also occur in humans [62]. Wide convergence of diverse inputs onto spinal neurons emerges as a prerequisite for their exibility and multifunctionality [153]. Do these alleged principles allow us to understand the operation of spinal networks and individual interneurons? The preceding discussion has tacitly followed an Ariadne thread originating from Sherringtons [340] concept of each component stretch reex being the self-operating reaction of an individual muscle (Section 4.1.2); it has thus primarily revolved around the local regulation of individual muscles or small groups of synergistic muscles, or of strict antagonist muscles around a single joint implicating reciprocal inhibition. Even under this restricted linear perspective, the stretch reex and its appendages (e.g., reciprocal and recurrent inhibition) appear to be engaged in a bewildering variety of different motor functions: generation of anti-gravity thrust and stiffness during stance, timing of sequential movement sections (e.g., locomotor phases), participation in the formation of movement trajectories, compensation for nonlinear muscle and musculoskeletal properties, stabilization of motor activities against internal perturbations (including muscle fatigue) and external perturbations. This is quite a kaleidoscope of functions, in which proprioceptive feedback has been supposed to be involved. Now multi-functionality probably is a characteristic of many neuronal networks, but whether these functions are at all and if so how compatible with each other has rarely been investigated, which remains a task for future conceptual and experimental work. Despite the complexity of many of the above functions and their subserving networks, they are still an oversimplication. This is because Sherringtons notion of reex standing as a harmonious congeries of stretch reexes is simply not true [137]. For the control of multiple-segment systems is much more complicated than suggested by Sherringtons notion, in that inter-joint coordination and intersegmental inertial interactions need to be mastered. It has been proposed that proprioceptive feedback acts to cope with these problems as well [140]. These issues therefore need to be addressed now. 9. Global roles of proprioceptive afferents Multi-joint systems pose severe problems. First, the positions and movements of different joints need to be coordinated, which leads into the issue of synergies and their neuromuscular organization (this main section). Second, more generally and abstractly, spatial relations of body parts require a central representation commonly referred to as body schema, which will be discussed in the context of postural adjustments (Section 10).

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Third, movements of coupled body segments depend on each other by inertial interactions, which have to be taken into account by the CNS in organizing movements (Section 11). 9.1. The redundancy problem The position of the index nger or paw endpoint in external space is specied in three dimensions. By contrast, the implementation of this position in terms of congurations of joint angles leaves much more freedom, in principle. Dependent upon the type of joint, the distal segment (bone) can be moved in up to three degrees of freedom with respect to the proximal one. Summing up the degrees of freedom of the joints participating in endpoint positioning may thus greatly exceed the number of external-space coordinates. This redundancy of possibilities holds for many postures and movements. The query for solutions to the redundancy problem [24] has to be conducted at various levels. 9.2. Global variables of limb geometry Consider the cat hindlimb with its three large joints: hip, knee and ankle joint. If, in a rst approximation, each of these joints is considered a hinge joint of one degree of freedom, allowing movements of the linked segments in a para-sagittal plane, then the limb would be a three-degree of freedom linkage of segments allowing for two-dimensional movement of the limb endpoint. Is this potential fully exploited? 9.2.1. Cat quiet stance When cats were trained to stand freely on a platform equipped with smaller force platforms, their quiet stance exhibited several strategic invariances. (i) When the whole platform was tilted forward and backward (pitch direction), the cats tended to keep the vertical orientation and the length of their limbs approximately constant. The orientation of the trunk remained roughly parallel to the surface, while the projection of the center of mass onto the support surface changed to some extent depending on tilt angle [199,201]. (ii) Loading the cats forequarters with 1020% of its body weight did not appreciably change the limb geometry in terms of length and orientation angle, despite a considerable forward shift in projection of the center of mass and an increase in contact force vectors (resultants of normal and tangential force vectors) at the front paws [199]. (iii) When cats were trained to stand with different distances between forefeet and hindfeet, the trunk remained oriented largely parallel to the support surface and the internal limb geometry remained about the same, although the limbs had to be levered at the girdles to accommodate the changes in foot distance. The direction of the ground reaction forces co-varied with the limb axes. The joint torques therefore remained the same in the forelimb, and varied only slightly in the hindlimb [106]. Contact forces and limb position appeared to be controlled independently of each other [197]. Finally and importantly, the values of the three limb joint angles, both of the fore- and the hindlimb, co-varied linearly in that they fell approximately into a two-dimensional plane within the three-dimensional joint space; the orientation

of this plane could vary with sensory (e.g., cutaneous) inputs [197]. Such ndings suggest that the maintenance of cat quiet stance requires an internal model of limb geometry in the framework of the body schema [197,200]. This model would serve as a reference to control actual body geometry. The models primary global variables appear to be limb length and limb orientation in space, which appear to be controlled independently of each other [224]. This amounts to a reduction in the number of the degrees of freedom, from the three limb joint angles to the two global variables, but also requires a transformation from the global polar coordinates into the local joint-angle coordinates. These global variables span a polar reference frame, much as in goal-directed arm movements in primates [115,345]. Most importantly, since spinalized cats can be trained to stand upright and walk on their hindquarters [83,103,107,317], the spinal cord alone must have an internal model of limb geometry in the framework of the body schema, however rudimentary. A spinal body schema is also required for the wiping reex of spinal frogs and the scratch reex of spinal turtles (Section 2). 9.2.2. Cat and human locomotion As during stance, one possibility to reduce the degrees of freedom during movement is to constrain the independence of movements in the different joints, i.e., to tightly couple changes in the three joint angles. This is indeed what happens during both passive and active cat hindlimb movements. The relationship among the three joint angles shows a planar or two-dimensional co-variation over a large range of limb positions [295]. In human locomotion, too, the elevation angles of the different segment motions are linearly related. The specic orientation of the plane in angle space reected the phase relations between the elevation angles and thus the timing of inter-segmental coordination [25,26]. This rule of planar co-variation reduces the degrees of freedom of lower-limb angular motions in the sagittal plane to two [198]. Similarly, in human reaching movements, segment excursions are coupled, and so are joint torques [367]. How is this reduction in degrees of freedom implemented? There are two main classes of constraint reigning in the degrees of freedom: biomechanical and neural. Biomechanical constraints are determined largely by visco-elastic properties of muscles and joint ligaments (next section), and neural constraints are co-determined by spinal reexes, such as group Ia and Ib pathways [106]. 9.2.3. Biomechanics In the passive limb, the mechanism underlying the joint-angle coupling is presumably of biomechanical nature, as indicated by post-mortem assessment. For example, biarticular muscles spanning two joints as well as passive structures such as ligaments may play a role in coupling different joints. During movements, inertial interaction forces (Section 11) may contribute to couple the movements of limb segments [32]. Moreover, several biomechanical mechanisms related to joint shapes, joint capsules and ligaments contribute to restrain the degrees of freedom.

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9.2.4. Neural control mechanisms As mentioned above, the hindlimb joint angles in quietly standing cats co-vary linearly. The specic pattern of joint-angle co-variance differs, however, from that in the passive limb. First, the coupling is tighter, suggesting that neural control may actually further reduce any independent motion in the individual limb segments. Second, the co-variance plane has a different orientation in three-dimensional joint space, due mostly to a sign inversion of the relationship between the hip and ankle angles [32,295]. The difference between the passive state and the active state implicates the CNS as a main player in determining the particular form of joint angle co-variation (the orientation of the plane in joint space). 9.3. Synergies The coupling of joint-angle rotations is often referred to as kinematic synergy. More generally, the notion of synergy can be discussed in three contexts: coordinated movements (kinematic synergy), muscle activations, forces and torques (kinetic or dynamic synergy), and neuronal circuits generating the preceding two [398]. As to the rst context, there is agreement that coordinated movement patterns in any task may be described as synergies (kinematic description). Now these kinematic synergies must be produced, at least in part, by activations of skeletal muscles. At this level, the problem is aggravated by the assertion that there are more muscles than needed to control all degrees of freedom in a task (overcompleteness or muscle redundancy). Bernstein [24] pointed out that the apparent redundancy might also allow for the great exibility of movement. More generally and abstractly, a principle of abundance has been suggested that states that all degrees of freedom always participate in all tasks assuring both stability and exibility [207]. In the concrete example of the human neckarm system, the number of skeletal muscles is actually close to that required to control all of the degrees of freedom, some of which may not be apparent in restrained experimental conditions and measurements [215]. In fact, synergies of muscles are often dened only relative to a particular axis of rotation of a joint [209,405]. Hence, the issue of whether task-dependent patterns of muscle activation, as assessed by electromyographic recordings, should be called synergies, is controversial in the current literature, and so is the role of proprioceptive feedback in organizing such synergies. In any case, a number of partially novel mathematical techniques have been used to identify and characterize muscle synergies in several species (e.g., frogs, cats, humans), movement paradigms (e.g., reexes, upright posture and its perturbations, locomotion, voluntary movements) and conditions [46,54,67,133,159,160,192194,369371,378]. Muscle synergies have been suggested to be related to highlevel, global, task-related variables important for movement control, e.g., ground-reaction forces in stance perturbations in cats [370], center-of-mass shifts in standing humans [192], foot and limb kinematics in walking [159,160], hand kinematics in nger spelling [378].

The neuronal systems involved in organizing synergies are complex and include locomotor CPGs (Section 3), sensory feedback (Sections 9.4.19.4.6), presynaptic inhibition (Section 9.4.6.3), recurrent inhibition (Section 9.4.7), and systems descending from supraspinal structures (Section 9.4.8.1). It appears that synergies utilize inborn neuronal networks as well as are acquired by learning (Section 12). In particular, exible changes in synergies often result from short-term learning [235]. In the present context, it is of importance to ask whether, and if so how, proprioceptive muscle afferents and recurrent inhibition could contribute to form such synergies. Proprioceptive feedback could play several roles with respect to synergies: (i) trigger synergies organized within the CNS (e.g., during corrective postural adjustments; Section 10), or (ii) adapt the recruitment of centrally organized synergies to behavioral constraints, or (iii) modify or ne-tune the activations of individual muscles within a synergy, or (iv) contribute to specify the synergies by re-organizing interneuronal networks, or (v) integrate itself with central circuits into large networks generating synergies as emergent properties [54]. 9.4. Involvement of muscle proprioceptors and recurrent inhibition in synergy formation The potential contributions of muscle proprioceptors to synergy organization may occur at different levels: (i) actions of individual muscles, (ii) actions of different muscles on individual joints, (iii) actions of multiple muscles on different joints. Thus, these contributions depend heavily on biomechanical factors, such as muscle structures and actions, which require a closer look. 9.4.1. Coping with muscle complexity Many macroscopically dened muscles are inhomogeneous as to their internal architecture, muscle ber composition, histochemistry, joint mechanics and reex connectivity [89,183,396]. They may exert several functions, either at a single joint with more than one degree of freedom or by spanning more than one joint. 9.4.1.1. Muscle regionalization. In many macroscopically dened muscles, the spatial distribution of the different types of muscle unit is non-homogeneous, to very different extents, though (muscle regionalization [183,376]. This is often correlated with a differential activation of different muscle regions in different motor tasks. In some cases, this heterogeneity is based on neuromuscular compartments, which are innervated by primary branches of the main muscle nerve and in some cases separated more or less clearly by tendinous sheets. Even individual compartments may show heterogeneous distributions of muscle-unit types and activity. In other cases, muscles are not compartmentalized and yet regionalized [69,89,183,396]. The location of different -motoneuron pools in the spinal cord is often (not always) somatotopically related to that of their muscles. As well, in many cases, the rostro-caudal location of -motoneuron somata within an individual pool may be somatotopically related to the location of

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their muscle units within the muscle. Different neuromuscular compartments may have different mechanical actions. For example, the compartments within the cat lateral gastrocnemius muscle exert torques in different directions at the ankle joint [48]. 9.4.1.2. Sensory partitioning and reex localization. Muscle spindles and Golgi tendon organs react sensitively to mechanical events in their local vicinity, and not only to muscle stretch, but also to contractions of the whole muscle or of muscle compartments or of individual motor units. The degree of discharge modulation, which a single motor units contraction produces, depends on the contractile strength of the motor unit and its relative location to the muscle spindle or Golgi tendon organ. This differentiated coupling between motor units and spindles or Golgi tendon organs has led to the concept of sensory partitioning. This in turn prompted the hypothesis of localized stretch (and possibly other) reexes [31,89,357,385,387,396]. In decerebrate cats, Cohen [59] showed that, when a thin muscle strip isolated from an extensor muscle (rectus femoris) was stretched separately, reex contraction was largely localized to that strip. Recent evidence for such reex localization was obtained in the medial gastrocnemius muscle of awake, standing cats [88]. The degree of reex localization varies widely across different skeletal muscles and depends on conditions. The cat semitendinosus muscle, which consists of two compartments in series to each other, shows no reex localization. By contrast, the cat splenius muscle, which is partially divided into serial compartments, does show reex localization [28]. This localization effect might be explained by assuming that the group Ia afferents of muscle spindles in a muscle region send the strongest monosynaptic projections to those motor units whose muscle bers are located in that region [31,387,396]. Moreover, other neuronal circuits, such as recurrent inhibition, might contribute to focus reex effects [37,386]. The functional signicance of reex localization in individual muscles remains unclear and requires more investigation [396]. In some respect, however, it is merely the single-muscle reection of a more general principle, namely the reex coordination of muscle elements exerting different actions. On a larger scale, for instance, the cat triceps surae muscle, consisting of the soleus and the medial and lateral gastrocnemii, extends the ankle. Their -motoneurons could therefore be expected to share reex connections from group Ia afferents in a divergenceconvergence pattern. On the other hand, the three muscles exert slightly different mechanical actions on the ankle joint, and very different actions on the knee joint because soleus does not span it. Thus, the group Ia connectivity should be differentiated according to the peripheral mechanical actions. 9.4.2. Coping with multiple degrees of freedom at a joint In contrast to the rst approximation used in Section 9.2, even the cat knee and ankle joints (quite apart from the hip joint) are no simple hinge joints but move in other directions than exion/extension, that is, abduction/adduction and ever-

sion/inversion, albeit to different extents. This is a case for Loebs [215] argument in Section 9.3. Importantly, these three degrees of freedom are not controlled each by a pair of antagonist muscles. For example, muscles acting across the cat ankle joint exert signicant torques in other directions than exion/extension and can in fact move the joint signicantly also in abduction/adduction and eversion/inversion directions [405]. For instance, the lateral and especially the medial gastrocnemius muscles exert large abduction and eversion torques in addition to their classical plantarexion torque. Only the anterior tibial muscle is a pure opponent to the gastrocnemii in all three planes. Similar considerations apply to the knee joint. For example, in the cat, the medial gastrocnemius muscle exes the knee and adducts it, while the lateral gastrocnemius exes and abducts it. The different torque directions may be utilized by the animal. During cat stance, abduction torques provide a component of the animals natural stance stabilization [221]. During locomotion, the substantial abductor torque of the medial gastrocnemius muscle could help turn the body to the contralateral side [270]. Similar mechanisms may be at work in humans walking along curvilinear paths [63]. 9.4.3. Intermediate summary The above examples sufce to stress the following points: (i) If the major degrees of freedom of a joint are kinematic variables to be controlled, an individual muscle or part thereof may exert actions on more than one variable (divergent actions). Conversely, any individual variable is inuenced by the actions of different muscles or parts thereof (convergent action). This implies that whenever an individual variable is to be changed alone (e.g., exion/extension), different muscles (and their inputs) must be activated and their actions must be precisely coordinated in a dynamic pattern. Thus, even the biomechanics of individual joints may require complex synergies of different muscles or parts of muscles. (ii) This problem is compounded at the level of multiple joints. Muscle action at one joint may inuence motion at another joint. This is self-evident in the case of bi- and tri-articular muscles spanning more than one joint. Even mono-articular muscles may exert dynamic actions on other joints by intersegmental interaction forces, however (Section 11). (iii) The action structure described above represents a multiple inputmultiple output (multivariable) system, which can be described by matrices transforming an input vector into an output vector. Such transformations are usually highly nonlinear and time-varying. (iv) If muscle proprioceptive afferents contribute to organize movements in multi-dimensional joint space, their reex connectivity patterns may be expected to reect the peripheral multivariable action structure in some way. (v) If there is any ground to believe that recurrent inhibition is functionally associated with muscle proprioceptive feedback (Section 4.3), recurrent inhibition should also exhibit a multivariable structure.

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These expectations are tested in the following by briey summarizing the connectivity patterns of proprioceptive afferents and recurrent inhibition. 9.4.4. Heteronymous connections of muscle spindle group Ia afferents While group Ia excitatory postsynaptic potentials are usually largest in homonymous -motoneuron pools (in particular in small -motoneurons), group Ia afferents make heteronymous monosynaptic connections to other -motoneurons [18,154,178,329]. Already in tortoise and turtle, heteronymous monosynaptic connections from low-threshold muscle afferents to motoneurons are quite strong relative to the respective homonymous connections [329]. Early electrophysiological work in anesthetized cats [82] showed that group Ia afferents from a particular cat hindlimb muscle connect monosynaptically to many species of -motoneurons across the limb, usually following the synergistic pattern [18,82,84,154]. These results, obtained with electrical nerve stimulation, were largely conrmed with more natural muscle spindle activation. In decerebrate cats, the stretch-evoked (length-dependent), short-latency excitatory reex effects in -motoneurons showed a clear pattern linking synergistic muscle groups, indicating that muscles with overlapping mechanical actions are linked by length-dependent excitatory pathways [268,384]. Some group Iamotoneuron connections linked muscles crossing different joints. But the latter seemed to be substantially weaker than autogenetic pathways or those linking muscles of synergistic groups [84,271]. Similarly, there are widespread and complicated heteronymous monosynaptic Iamotoneuron connections in the cat forelimb [43,104], with many cross-joint connections, as well as in the human lower limb and arm [178,230,231,255]. In addition to monosynaptic group Iamotoneuron connections, oligosynaptic pathways may contribute to heterogenic links. During the extension phase of cat ctive locomotion, stimulation of extensor group I afferents elicited widespread disynaptic excitatory postsynaptic potentials in -motoneurons innervating extensor ankle, knee and hip muscles, albeit in an asymmetric pattern [9]. At rst glimpse, therefore, these heteronymous connections appear well suited to contribute to the organization of muscle synergies. As much as excitatory monosynaptic Iamotoneuron connections link synergistic muscles, disynaptic reciprocal Ia inhibition links groups of antagonistic muscles, the pattern of distribution largely resembling that of Ia synergism except that, in the cat hindlimb, no reciprocal Ia inhibition exists between abductors and adductors [154,329]. The pattern of reciprocal inhibition is more complicated, however, when bi-articular (bifunctional) muscles are involved [327]. 9.4.5. Heterogenic connections of muscle spindle group II afferents Another system with a potential for contributing to inter-joint coordination is the reex system established by group II muscle afferents.

In reduced cat preparations, group II afferents from one muscle have widely divergent excitatory and inhibitory effects on -motoneurons innervating muscles throughout the hindlimb, and each -motoneuron pool may receive convergent actions from group II afferents from various muscles, with the patterns depending on animal state. Because of this complex network with several internal specializations, group II spindle afferents have been proposed to be involved in more global features of motor coordination across a whole limb [164,329]. Precisely what the global features are, and exactly how group II spindle afferents contribute to regulate them, remains to be claried. In humans, too, widespread group II afferent connections exist between -motoneurons innervating muscles at the foot, upper and lower leg. These have been interpreted in the context of human bipedal stance and locomotion [229,232,341]. 9.4.6. Heterogenic connections of Golgi tendon organ afferents Heterogenic reex effects from group Ib afferents onto motoneurons again vary with motor state and task. 9.4.6.1. Quiescent state. In reduced immobile cat preparations, electrophysiological studies revealed that, for example, group Ib afferents from an extensor muscle exert reex effects on almost all -motoneuron pools of the ipsilateral limb [154,163,164,329]. In decerebrate cats, the distribution of shortlatency force-dependent inhibitory feedback between ankle and knee muscles was complex and asymmetric, but showed a pattern that was largely complementary to the distribution of fast excitation (Section 9.4.4). This pattern of distributed heterogenic force feedback, linking muscles acting across different joints and axes of rotation, has been suggested to help coordinate joint movements in the major degrees of freedom [268,271,384]. 9.4.6.2. Stance phase. During quiet stationary stance in normal cats, the excitation of Golgi tendon organs by means of intramuscular muscle stimulation and consequent twitches produced reex effects in -motoneuron pools innervating muscles across the hindlimb [297]. In pre-mammillary decerebrate cats walking with three legs on a treadmill and the fourth (hind)limb immobilized for reex studies, force-related feedback was positive only in autogenic reexes (from medial gastrocnemius onto itself), while heterogenic force feedback to other ankle extensor muscles was still negative, like at rest [312,313]. The contrast to other studies might be due to differences arising from electrical versus natural (e.g., stretch) stimulation (T.R. Nichols, personal communication). In retrospect, these results question the basic assumptions of pure positive force feedback in the model of Section 6.1, but may complement it by introducing possibly stabilizing inhibitory force feedback. It has been argued that the distribution of fast heterogenic force-dependent inhibition seen in quiescent preparations as described in the previous section (Section 9.4.6.1) may not be at variance with the positive force feedback in extensor muscles during stance, but may serve to coordinate them, whereby

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these two mechanisms would operate in conjunction [384]. The precise way they do remains to be determined. 9.4.6.3. Potential role of presynaptic inhibition in synergy formation. Presynaptic inhibition co-organizes the functional connectivity between sensory afferents and -motoneurons in a state- and task-dependent manner (Section 5.2). In analogy to other reex pathways reviewed above, sensory afferents evoke presynaptic inhibition of sensory afferents according to a matrix connectivity pattern. An example of heterogenic cross-joint action of presynaptic inhibition is as follows. In decerebrate cats, group Ia afferents from the quadriceps muscle presynaptically inhibit the soleus H reex during the stance phase of locomotion, thereby potentially reducing the efcacy of the soleus stretch reex when the muscle yields in early stance [256]. On a ner scale, presynaptic inhibition may contribute to the organization of changing synergies via muscle afferents, provided its effects on afferent terminals are differentiated according to the afferent targets. In fact, there are various pieces of evidence supporting such a target-specic differentiation [165]. First, different terminals of the same group Ia afferent, e.g., on -motoneurons and dorsal spinocerebellar tract neurons, may be controlled by different sets of presynaptically inhibiting interneurons. Second, group I afferents from the same muscle can display different patterns of locomotor phase-dependent primary afferent depolarization [317]. Third, presynaptic inhibition of group II afferents is much stronger on terminals in the spinal intermediate zone than on those in the dorsal horn, this differentiation being potentially supported by differential effects of noradrenaline or serotonin [165]. Fourth, in humans performing voluntary ankle or knee contractions, presynaptic inhibition of group Ia afferents may differ on homonymous versus heteronymous terminals [155]. In principle, therefore, the differential action of presynaptic inhibition on different terminals of the same afferent could help organize shifting synergies. 9.4.7. Heterogenic connections of recurrent inhibition In the cat hindlimb, recurrent inhibition is particularly strong between -motoneuron pools innervating close synergists and is absent between -motoneuron pools innervating strict antagonists, but it links more -motoneuron pools, some of which are located in different spinal segments and innervate muscles on different limb segments. These connections are not always symmetrical, i.e., one -motoneuron pool may recurrently inhibit another, but not vice versa, or the reciprocal connections differ in strength. Essentially the same holds for the cat forelimb. The recurrent inhibitory connections between -motoneuron pools are more complex than in the hindlimb, however [154,178,391]. The general sketch pictured above also applies to humans. As compared to the cat, however, trans-joint recurrent inhibitory connections occur more frequently in man, and they may even affect antagonist -motoneuron pools. The recurrent inhibitory connections among -motoneuron pools of the human arm are complicated, too, but trans-joint connections are more restricted [178].

9.4.8. Comments The divergenceconvergence patterns existing in reex connections from muscle proprioceptors to -motoneurons, in presynaptic inhibition and in recurrent inhibition conrm the expectations expressed in Section 9.4.3. An important point to emphasize is that all the above-described patterns are instances of transformation networks, performing spatial transformations, kinematic-to-kinetic and kinematic-to-kinetic transformations, as required in Section 2. The monosynaptic Iamotoneuron connectivity patterns described in Section 9.4.4 are sometimes referred to as Ia synergism [43,104,329]. Although this parlance may be taken as operational shorthand, it tends to insinuate the notion that such patterns were prominent in organizing muscle synergies for motor acts, such as locomotion and the performance of skilful grasping movements. The underlying idea is that the fusimotor system distributes excitation to muscle spindles and these via group Ia afferents to synergistic pools of -motoneurons. While, by virtue of their very existence, divergent Iamotoneuron connections may play a role in synergy formation, any hypothesis claiming that synergy formation is their major function must specify this role and answer a few questions. (i) Why is a complex reex system needed to generate synergies, or is there something special about the reex aspect? (ii) Since it is ultimately the -motoneurons that distribute excitation to -motoneurons and must thus be coordinated synergistically, where does this input synergy come from; and if it comes from the usual suspects, such as the locomotor CPG, descending and afferent inputs, why do these systems not directly affect motoneurons, which indeed they do, as a matter of fact (below)? (iii) What is the specic role of Ia synergism among the other synergy-forming systems, central and reex? 9.4.8.1. Synergy formation by other systems. First, as mentioned in Section 3, segmental pattern-formation networks (which may be considered belonging to the locomotor CPGs) distribute spatio-temporally ordered excitation and inhibition to -motoneuron pools. These synergy-formation networks are powerful and in principle independent of descending inuences and sensory feedback, although the latter modulate the locomotor CPG patterns and may reset their rhythm. Second, as much as locomotor CPGs receive modulating and control signals from supraspinal structures, these signals co-organize muscle synergies by-passing CPGs. For example, there is a similarity between the organization of group Ia feedback and cortico-motoneuronal control of motoneurons (most of the motor cortical output projecting to supraspinal structures, though). In primate evolution, pyramidal tract neurons have increasingly developed divergent monosynaptic connections with different synergistic -motoneuron pools involved in precise manipulative movements. It also appears that cortico-motoneuronal cells project to almost all the -motoneurons in one pool as do group Ia afferents. Conversely, each -motoneuron pool receives inputs from different cortico-motoneuronal cells, which are clustered in multiple distinct cortical loci. These two features then make up the familiar divergenceconvergence pattern [97]. Moreover, many

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forearm cortico-motoneuronal neurons project to antagonistic -motoneuron pools in a reciprocal way, facilitating extensors and inhibiting, via interneurons, exors, or vice versa [53]. This system organization may be used in a functionally signicant way by specifying task- and context-dependent muscle synergies [323]. Other descending systems also show such divergent distribution patterns, e.g., the reticulospinal system [237], the rubrospinal system [11,52], and the cervical propriospinal system [6,290]. Third, as discussed above, there are other afferent sensory systems that have been considered as supporting muscle synergies, such as feedback from group II muscle afferents and group Ib afferents, and ultimately reciprocal inhibition and recurrent inhibition. Finally, there are notable exceptions to Ia synergism. For example, although the -motoneurons to exor hallucis longus and exor digitorum longus in the cat hindlimb share mutual monosynaptic group Ia excitation, they exhibit exclusive activity patterns during normal locomotion [40]. This re-emphasizes the importance of spinal locomotor CPGs in organizing spatiotemporal synergies of muscle activations. 9.4.8.2. Flexible synergies. Synergies of muscles or parts thereof may change within a motor task and between motor tasks, implying that the organizing structures should be exible as well. Hence, monosynaptic Iamotoneuron connectivity patterns should be exible. In principle, such exibility could be afforded by varying fusimotor actions and/or presynaptic inhibition. It has been argued that fusimotor spindle innervation is not able to differentiate between the group Ia projections to different muscle groups [329]. This argument presumes homogeneous Ia afferent outow from a muscle, but may not hold for functionally differentiated muscles, in which different regions exert different actions and different regional muscle spindles might receive different fusimotor inputs (Section 9.4.1). Furthermore, the pattern of Ia synergism may be adapted to the specic requirements of different motor tasks by presynaptic inhibition, whose patterns of action are co-determined by inputs from descending tracts and various segmental afferents converging onto the interneurons mediating presynaptic inhibition (Section 5.2). Thus, if presynaptic inhibition helps adapt Ia synergism to current motor task and prevailing circumstances, the synergism is actually organized, or at least modulated, by another system than by Iamotoneuron feedback. In summary, synergy formation appears too important a function as to leave it to Ia synergism alone. As well, the monosynaptic Iamotoneuron connections must be revised in the context of oligo-synaptic Iamotoneuron connections (Section 5.7.3), whose relative role in synergy formation is not clear at present. 9.4.8.3. Monosynaptic Iamotoneuron connections and recurrent inhibition. In the cat hindlimb, the distribution of heteronymous RI exhibits a striking overlap with that of heteronymous monosynaptic Ia excitation. . . ([178]; pp. 337338). Such a similarity has been suggested to exist both

for animals [391] and humans [178], but there are also large discrepancies. It has been proposed that, because of the similarity of distributions of heteronymous recurrent inhibition and monosynaptic Ia excitation, . . .the recurrent inhibitory system may limit the extent of Ia excitatory effects to MNs ([178], p. 338). This is just one among several similar ideas ascribing limiting functions to recurrent inhibition [387,391], these ideas essentially following the line of thinking discussed in Sections 4.2 and 4.3: The functionally sensible introduction of one circuit may cause a new problem, calling for another circuit to solve it. But in comparison to reciprocal inhibition (Section 4.2), the situation is different with respect to recurrent inhibition and prompts questions. Why should Nature invent a complicated system to reign in excesses of another one? Why could monosynaptic Ia feedback to -motoneurons not be properly tuned right away, by appropriate scaling of fusimotor control and synaptic strength? Why should recurrent inhibition be imposed upon an already existing and apparently successful limiting system, the phylogenetically older presynaptic inhibition? Before these questions are plausibly answered, the above suggestion appears to violate the principles of Ockhams razor, parsimony and simplicity of explanation [391]. Incidentally, this suggestion adds just another system controlling Ia synergism, thereby questioning the latters prominence in synergy organization (Section 9.4.4). Perfect isomorphy of the inter-motoneuronal distribution patterns of group Ia afferents and recurrent inhibition cannot be expected. Since, as outlined in Section 4.3.1, recurrent inhibition prevails among -motoneurons of more proximal muscles, which play a greater role in posture and locomotion, a closer match should exist among proximal muscles. Whether the distribution patterns of recurrent inhibition and muscle spindle Ia afferent connections are matched in some way to the intermotoneuronal distribution of the positive force feedback system is not known because the latter has not yet been investigated as carefully in quantitative terms. Does recurrent inhibition contribute to muscle synergies? Probably it does, by virtue of its very distribution. Is this contribution the function of recurrent inhibition? It may be a subsidiary, but probably not its primary function. There are already several central and reex systems organizing muscle synergies; addition of yet another one for the same purpose does not seem to make much sense. There must be more to recurrent inhibition. In summary, what Ia synergism actually does in freely moving intact animals is an open question. In general, synergy formation is likely to be the coordinative function of several systems, with any one making its own special contribution. It is fair to state, however, that we are far from understanding these special contributions and their interactions, which to elucidate may be impossible with the currently available techniques. 10. Postural maintenance and adjustments Upright posture of animals standing on legs is a shaky condition, particularly in two-legged animals, such as humans and birds. It is always jeopardized by internal and external inuences, permanently by gravity, and thus necessitates continuous

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stabilization. Despite its name, stabilization of static equilibrium is a dynamic process because the body is always in motion and keeping the center of gravity above the support base therefore requires continuous, more or less large postural adjustments. These adjustments have to be organized with respect to a reference, which very generally can be designated as body schema. 10.1. Multiplicity of body schemata While the conscious experience of corporeal awareness suggests a single unied body schema, there are several schemata. Head and Holmes [141] postulated one schema for each major sense, including tactile sensation, kinesthesia and vision, which can be probed independently but must be fused at some stage (see also [110]). Some schemata may be used subconsciously for motor control. Body schemata are important for organizing both static posture (Sections 10.210.5) and dynamic movements, such as wiping and scratch reexes (Section 2), and voluntary movements (Section 10.6). It merits re-emphasis that, since spinalized cats can be trained to stand upright and walk on their hindquarters, the spinal cord alone must be able to construct a body schema, however rudimentary (Section 9.2.1). 10.2. Postural body schema It has been argued above (Section 9.2.1), that the maintenance of cat quiet stance requires an internal model of limb geometry in the framework of the body schema. This holds more generally and also applies to humans. The postural body schema incorporates a representation of verticality. The CNS organizing upright stance needs requisite information on the earth vertical, with which the body can be aligned. A number of potential sources of information exist for the CNS to specify the bodys postural orientation with respect to the external world (for details see refs. [236,252]): Proprioceptive signals, originating around the ankle joints (from muscle spindles, joint receptors, etc.) could indicate whether the body is perpendicular to the (level) ground or not. If the CNS uses signals from muscle spindles in active muscles, it is confronted with the problem of extracting the position-related signal from the compound signal, which also contains a fusimotor-induced activity component [305]. Moreover, load receptors in joints could collect information about the vertical gravity axis. Cutaneous signals from the foot soles, indicating the distribution of pressure, could be evaluated so as to indicate whether the body is perpendicular to the (level) ground or not. Graviceptive information. Psychophysical evidence suggests there to be graviceptors in the trunk, whose activity indicates the earth vertical [257,258]. Vestibular signals provide indications of the heads position and movement in external space. Visual information. Whenever the visual surround is stationary and the linkages between the head, trunk and legs are rigid, visual motion could signify motion of the body in space.

Obviously, in intact animals the construction of the postural body schema is a complex process requiring the interaction of several senses, the intricacies of which are beyond the scope of the present review. The spinal body schema in spinal cats must dispense of vestibular and visual information and still works reasonably well, having to rely primarily on proprioceptive and cutaneous information. In the following, therefore, these sources are in the focus. Group Ia afferents exert a strong inuence on the postural body schema that, as a reference, indirectly inuences posture. Muscle vibration, which if calibrated carefully primarily excites group Ia afferents, should thus affect both the conscious body schema (by producing illusions of body motion; [110]) and posture. In fact, vibration of various muscles along the body makes a subject lean in directions depending on the muscle(s) vibrated [179]. 10.3. Role of proprioceptors in human body sway From perturbation experiments in humans, it was concluded that proprioceptive signals from the leg muscles operating at the ankle and the evoked reex changes in muscle activity were sufcient to support the human body during standing [101]. In particular, (ii) the low reex-loop gain of around unity implied that, in a range <2 Hz encompassing postural sway frequencies, the average sway amplitude was reduced to about half of that without sensory feedback; (ii) during standing, perturbation-evoked soleus electromyographic activity showed a phase advance to ankle movement increasing with frequency. Such a phase advance is opposite to the phase lag expected from a reex response with delay. Phase advances of ankleextensor muscle activities to sway have been observed in other experiments [113,219,326]. Pertinent questions arising include: (i) Which sensory systems are involved in the reex responses of ankle extensor muscles to sway? (ii) Specically, do spindle group Ia afferents contribute signicantly to this sensory feedback? (iii) How does the phase advance of ankle-extensor muscle activity versus sway come about? 10.3.1. The case against group Ia afferents While the velocity sensitivity of group Ia spindle afferents does not appear important during slow postural sway, the length sensitivities of both group Ia and spindle group II afferents detect the low-frequency displacements occurring mainly about the ankle [134,259]. Studies on human neurological patients have provided evidence, however, that the monosynaptic stretch reex involving group Ia spindle afferents does not contribute much to the stabilization of postural sway. In patients with Charcot-Marie-Tooth type 1A disease, featuring a severe loss of large-diameter nerve bers, the body sway area during quiet stance was within the normal range in the less severely affected patients, but was moderately increased in the more severely affected patients. Thus, the largest nerve bers (motor and sensory) do not appear necessary for appropriate equilibrium control during quiet stance [267]. In these

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patients as well as in diabetic patients with an additional loss of smaller bers, the loss of motor bers and ensuing reduction in leg muscle strength was not detrimental to stance stability, suggesting that fairly little force is needed to maintain stable upright stance [266]. Diabetic patients with polyneuropathy oscillated more severely than did normal subjects [70,266]. This increase in postural sway was most likely related to a loss of sensory bers, in particular in distinction to Charcot-Marie-Tooth type 1A patients to a loss of spindle group II afferents [266]. Furthermore, as discussed before (Section 5.2), the efcacy of stretch reexes depends on, among many other factors, presynaptic inhibition, which may suppress the synaptic efcacy of segmental afferents. There is evidence that the synaptic transmission from group Ia afferents to -motoneurons is presynaptically inhibited during stance, and even more so during locomotion [177,266,351]. In summary, the monosynaptic stretch reex involving group Ia afferents does not appear to play a major role in generating moment-to-moment compensation for postural sway. This would most probably also apply to reciprocal inhibition and recurrent inhibition, as well as to monosynaptic group IImotoneuron connections, which are weak anyhow (see Section 4.1.2). 10.3.2. Alternative sensory afferents involved in sway control Thus, spindle group II afferents might contribute to stabilize quiet upright stance, but exactly how they do so remains to be determined. Moreover, as mentioned above, Golgi tendon organs may contribute to stance regulation via medium- or long-latency reex pathways in cats and humans [77,297]. Finally, cutaneous mechano-receptors in the foot sole could play an important part in detecting and monitoring body sway [180,223]. Rather than measuring sway directly, these receptors would monitor components of the ground reaction force that are affected indirectly by the sway movements [259,260]. In fact, articial stimulation of cutaneous tactile inputs from the foot soles elicited postural adjustments [181]. 10.4. Role of proprioceptors in human postural reactions

responses involved activation of spindle group II afferents affecting -motoneurons through a lumbar interneuronal network. The amplitude of the medium-latency response, but not that of the short-latency response, changed with postural set in that, for example, it was reduced when the subjects held onto a stable frame rather than standing freely [34]. Proprioceptors responsive to early stretch or release of paraspinal, pelvic and hip muscles may be instrumental in triggering postural reactions whenever roll trunk movements are involved. In fact, stretch reexes in these muscles have latencies as short as 25 ms. Even neck muscles react to perturbations at latencies shorter than those of ankle muscles [47]). In patients with Charcot-Marie-Tooth type 1A disease with absent or markedly reduced lower-limb tendon reexes, the short-latency responses and medium-latency responses to stretch in a foot muscle were absent and delayed, respectively [267]. Similarly, patients with subtle diabetic neuropathy, who had no monosynaptic Achilles reexes and weak or no patella reexes, displayed relatively normal postural strategies and synergies, albeit with some changes in timing and amplitude [266]. In other studies, balance-correcting responses in tibialis anterior muscle were diminished and delayed, but prominent responses remained in the soleus, gastrocnemius, quadriceps, paraspinal and trapezius muscles. These ndings indicated that pitch balance-correcting responses were predominantly triggered by proprioceptive afferents from hip and knee exor and extensor muscles and to a much lesser extent by proprioceptive afferents from the lower legs. In particular, group Ia afferents are not essential for triggering balance-correcting reactions [133]. In humans and non-human primates, the segmental stretch reex is supplemented by long-latency reexes, one or the other of which traverses the cerebral cortex [240]. While the latter were formerly supposed to be particularly well developed in arm (specically hand) muscles that are under strong cortical control, they have been suggested to also occur in lower-limb muscles [57]. All in all, the classical neurophysiological analysis of stereotyped reex action in the cat, decerebrate or otherwise, failed to alert us to the complexities of the human stretch reex ([240], p. 91). 10.5. Automatic postural responses in cats

The situation might be different during more severe perturbations of quiet stance. When the support surface under a quietly standing human subject was suddenly rotated in the pitch or roll direction, the postural reaction appeared organized according to two separate synergies, the reaction to pitch tilt by muscle actions around the ankle and knee joints, the reaction to roll tilt around the hip and lumbo-sacral joints [133]. In normal subjects, pitch tilt (toe-up rotation) of a supporting platform elicited short-latency responses and medium-latency responses to stretch in the soleus muscle (at latencies of 40 ms and 66 ms, respectively) and in a foot muscle [34,267]. While the short-latency response was most probably a typical stretch reex mediated by group Ia afferents and their monosynaptic linkages to -motoneurons, there was evidence that the medium-latency

Insights into balance maintenance can also be gained from normal and treated cats standing quietly when their support surface is suddenly moved. When normal cats stood quietly, with their feet on four small force platforms mounted on a movable platform, sudden horizontal translations of this platform generated typical postural reactions. Initially, the feet moved with the surface while the trunk remained behind due to inertia. Thus, the major joint-angle changes occurred at shoulders and hips and at the metacarpo- and metatarso-phalangeal joints. Such surface displacements evoked responses, which consisted of spatial and temporal patterns of muscle activation and inhibition as well as of the resultant active ground force vectors, all of them specic to the direction and velocity or acceleration of the disturbance [146,368,369]. In

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such intact cats, ve basic muscle synergies were identied in response to different types of postural perturbation. Since these synergies were robust to different perturbations evoking widely differing sensory inputs, it was argued that they did not arise from biomechanical constraints or from reex pathways, but rather represent a central mechanism [370]. Adult spinal cats can be trained to stand for a short while, attesting to the spinal cords ability to generate weightsupporting extensor activities. Such cats were severely impaired in maintaining balance, however. In particular, spinal cats lacked the typical, appropriately timed automatic postural responses of the normal cat to stance perturbations. The two functions of weight support and balance maintenance thus appeared to be controlled by different mechanisms and by different regions of the CNS. The residual stability in the spinal animal likely relied on the inherent stiffness of the tonically active extensors as well as on spinal reexes. In fact, as compared with the intact animal, mono- and polysynaptic reexes were enhanced in the chronic spinal cat [222]. By contrast, the neural circuits controlling balance extend beyond the spinal cord. This is also indicated by the nding that postural reactions similar to those in intact standing cats, albeit less robust, can be obtained in decerebrate cats [145]. It is well known that the preservation of good balance requires the integration of visual, vestibular, and proprioceptive information [146]. The brainstem and/or cerebellum are likely candidates for this integration because they receive afferent signals from the above sensory systems, and they might be involved in formulating an internal model of body posture [222]. As argued above, however, the spinal cord alone should contain an at least rudimentary model of limb geometry (Section 9.2.1). Which receptors trigger the postural responses? In response to stance perturbations, many different somato-sensory receptors are activated, including proprioceptors in muscles and joints and cutaneous mechanoreceptors, especially in the paw pads. Any of these sensory inputs could contribute to reex activation of the tonically active extensors (Section 5.7). The directional tuning of the automatic postural responses has been suggested to depend on the ratio of shear to load reaction forces at the paws, and the forces to be monitored by cutaneous afferents in the foot soles in a way similar to the ratio of slip to load forces during grasping nger movements [368]. The effects of loss of large-diameter sensory afferents underscore their signicance for automatic postural reactions. For example, cats treated with overdoses of pyridoxine (vitamin B6) and exhibiting a loss of large-diameter cutaneous and muscle afferents, showed large delays in automatic postural reactions, making them ataxic and prone to fall or step frequently [348]. The precise role of different somato-sensory receptors in balance reactions of the cat needs further dissection. 10.6. Anticipatory postural adjustments to self-generated movements . . . every movement necessarily begins and ends with a postural adjustment ([71], p. 33). While standing, movements of body segments such as the arms or legs will change the distri-

bution of mass and thus the position of the center of mass with respect to the support surface, as well as exert inertial interaction forces between the body segments depending on the movement velocity and direction (Section 11). In order to preserve equilibrium, the CNS must take these actions into account in advance, in a way precisely calibrated to movement direction and velocity. Anticipatory postural adjustments are thought to be generated centrally involving the spinal cord, without much inuence of sensory feedback from the periphery [71]. One neuronal substrate for postural adjustments accompanying arm movements could be descending axons of cervical propriospinal neurons [290]. 11. Proprioceptive feedback in intersegmental interaction dynamics Since body segments are movably coupled at the joints, they exchange potential and kinetic energy throughout a movement, with energy owing into or out of the segments. This has at least two implications. (i) An external perturbation impinging on one segment will also act on others. (ii) The actions of skeletal muscles on movements are often derived from their anatomical sites of origin and insertion. This notion is oversimplied and essentially wrong, however. The force a muscle generates accelerates not only the segments of origin and insertion, but also all other segments and joints via intersegmental interactions [407,408]. In organizing dynamic movements, the nervous system must take these interactions into account. The extensive convergence divergence structure of proprioceptive reex actions on motoneurons (Section 9.4.3) appears well suited to contribute to this task. Consider a few examples. 11.1. Cat paw shake During the cat paw shake, the intersegmental dynamics are very complex. Specically, hip muscles produce torques that counteract distal accelerations and postural torques. At the knee, large torques related to paw angular acceleration dominate interactive contributions to the net knee torque, which are nearly counterbalanced by muscle torques. By contrast, at the ankle, muscle torques dominate and directly inuence ankle dynamics. Knee stabilization by muscle activity derives at least in part from proprioceptive feedback. This is indicated by the fact that articial limb immobilization by a plaster reduces knee extensor activity, and an increase of the paws mass disrupts knee extensor activity and lowers the paw-shake frequency [344]. Furthermore, in chronically spinalized cats, half of the paw shakes show coupled ankle and knee oscillations, while half disorganize into uncoupled ankle and knee oscillations, which has been taken to indicate that motion-dependent feedback is necessary to stabilize inertial effects due to large ankle joint accelerations [190]. Of major importance in this context could be signals from ankleextensor group Ia afferents [303,344]. Thus, in the case of the paw-shake response, afferent signals play an important role in stabilizing the knee, which entails solving the dynamics problem presented by inertial interactions ([140], pp. 209210). This is a specic, task-dependent solution, though.

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11.2. Cat walking As mentioned earlier (Section 5.5.1), cats whose triceps surae muscles in one hindlimb had been denervated and allowed to self-reinnervate (re-establishing motor, but not sensory muscle innervation) showed severe decits while walking down a ramp when the triceps surae muscles normally undergo lengthening contractions. In addition to the strong yield of the ankle joint, the coordination of ankle and knee movements was disrupted [1]. This dis-coordination could have resulted in part from disruption of intersegmental dynamics and in part from the lack of proprioceptive muscle afferents to knee muscles [1,84]. However, the kinematic near-normalcy of level and uphill walking relegates heteronymous reex connections to a less signicant role. 11.3. Human arm reaching During arm movements, dynamic interactions between the segments vary with movement direction and require different muscle activation patterns for compensation. Neurologically normal human subjects could adapt their muscle activation patterns so as to take account of the changing interaction torques [127]. By contrast, human patients suffering from a loss of largediameter sensory afferents exhibited characteristic movement errors. These resulted from a dissociation of elbow and shoulder movements due to an inability to program elbow muscle contractions so as to account for elbowshoulder interaction torques. After practice under visual control, the movement errors diminished. Such results were taken to indicate that (i) the planning and learning of movement require an internal model of the limbs dynamic properties including interaction torques; (ii) this internal model is normally built and updated using proprioceptive signals; (iii) the lack of proprioceptive afferents can be partially compensated for by vision of limb motion [116]. One suggestion holds that the internal model of limb dynamics is computed with neurons encoding the limb state in a manner similar to that of muscle spindle afferents [157]. Movement trajectories of the wiping reex in spinal frogs are also distorted after de-afferentation. The disturbances resemble those seen in de-afferented human patients and have been ascribed in part to a loss of regulation of interaction torques at hip and knee [176]. It has been hypothesized that the pattern of long-latency reexes to external perturbations seen across different joints mimics the pattern normally occurring for unperturbed voluntary movements. For instance, if at the elbow joint the forearm is perturbed into extension, intersegmental interaction would ex the wrist. Intuitively, one might expect that corrective reexes would ex the elbow and extend the wrist again, but this does not occur because long-latency reexes activate wrist exors together with elbow exors. Hence, counter-intuitively, the passive mechanical perturbation at the wrist is supported by the long-latency reex, which provides an example of a de-stabilizing reex response. The functional rationale might be that the long-latency reex circuits normally support voluntary movements. That is, during voluntary elbow exion, passive wrist extension via inter-

segmental interactions could be prevented by concomitant wrist exor activation using long-latency reex circuitry [138] (see also [117]). This would require an early up-regulation of this circuitry. 11.4. Comments Clearly, the neurological loss or articially caused (e.g., pyridoxine-induced) ablation of large-diameter sensory afferents indicates that these afferents play a role in organizing intersegmental interactions, and in part this organization occurs at spinal level, as indicated by results from spinal frogs [176]. . . . there is pressing need to reconcile this purported mechanism with what is known about the synaptic connections of proprioceptive afferents to motoneurons that have their effects on neighboring joints as well as their own joint ([140], p. 210). Has any major progress been made to full this need? Doubt is warranted. Precisely which afferents are most important, and where in the neuraxis and exactly how they exert these inuences is not yet clear. This is due in large measure to the technical difculties in experimentally measuring these effects in freely behaving animals. In any case, the precise way that proprioceptive feedback contributes to solve the dynamics problem presented by inertial interactions is bound to be complicated and task-dependent, allowing the CNS to counteract or exploit inertial interactions in movement, depending on the prevailing circumstances. It is very unlikely that stereotyped spinal reex connections alone could full this role, but modulation and gating of these connections by descending, and possibly afferent, pathways could accomplish the task in conjunction with descending feedforward control of -motoneurons based on adaptable and learning internal models, in whose establishment and maintenance the cerebellum might play a major role [116]. 12. Plasticity, adaptability and learning Obviously, the CNS must adapt its actions to changing conditions of the environment, including its own body, and learn from their effects, at very different levels of organization and time scales. This requires its neuronal networks, including reex pathways, to be plastic rather than rigid. In a narrow behavioral sense, motor learning implies the acquisition of new behaviors or skills by practice [79]. But the term is often used with wider connotations including processes and mechanisms at much lower levels of complexity. The structures subject to plasticity are manifold and distributed throughout the neuraxis, even extending to the neuromuscular junction [333]. 12.1. Learning kinematics and dynamics There is no clear experimental evidence as yet as to whether the CNS explicitly plans movements in kinematic or kinetic (dynamic) terms [367]. In addition to the possibility that it does so in either kinematic or dynamic variables, it could do both or neither [346]. There is some evidence to indicate, however, that there are separate internal models for kinematic

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and dynamic control of reaching, which can be learned independently. It has been suggested that hand kinematics are learned from errors in direction and extent of movement in an extrinsic coordinate system, while dynamics are learned from proprioceptive errors in an intrinsic coordinate system [191]. Furthermore, experiments on freely standing cats showed that joint torques and contact forces at the paws varied independently of limb geometry, suggesting that the two sets of kinematic and kinetic variables were controlled independently by the CNS [197]. It has also been proposed that kinematic goals are specied at higher levels in a hierarchical organization, and are transformed into dynamic motor commands at lower levels [295]. Arm movements can be made in largely varying conditions, to which they can adapt if changing [196,337,401]. These changes may involve varying external forces or internal intersegmental dynamics. Studies in humans with changing inertial loads on the forearm indicated that adaptation involves three sequential processes: an initial anticipatory process based on an internal model of limb dynamics, error correction and postural control. The latter two processes require proprioceptive feedback, but proprioceptive signals are also used to update and maintain the internal model. Exactly where and how these processes are implemented is not yet known, however [322]. The internal model of limb dynamics has often been located to supraspinal structures, in particular the neocortex and cerebellum [182,191,196,337,402]. Since the spinal cord of some preparations is able to organize well-behaved dynamic limb movements, however, some at least rudimentary internal model of limb dynamics should also exist in the cord. An excellent case for the capability of the spinal cord to learn kinematics and dynamics is the restoration of function after spinal injury and neurectomy. 12.2. Restoration of function after spinal cord injury Even the spinal cord is able to learn and memorize [399,400]. This is indicated by the fact that spinalized cats can be trained to stand with their hindlimbs (above) and walk on a treadmill (below). Furthermore, the lower spinal cord of such cats remembers stumbling. When a swinging hindlimb meets an obstacle, it will produce stronger exions during the following steps in the absence of the obstacle. These short-term learning processes may be supplemented by longer-lasting processes [83,103,400]. Adult cats that are completely spinalized at low thoracic level re-learn within weeks to walk with their hindlegs on a treadmill. While the kinematic patterns look nearly normal, there are decits due to the absence of voluntary and reduced equilibrium control, and changes in exor muscle synchronization may lead to foot drag. While some recovery of walking appears spontaneously, locomotor training on a treadmill can increase the maximal speed achievable and the length of steps, improve limb coordination and thus reduce asymmetrical steps and stumbling. This re-learning is task-specic in that the spinal cats trained to simply stand are worse at walking, and vice versa. The learning effect may get extinct over several weeks after cessation of training but can be re-acquired rapidly. In these completely

spinalized animals, there is no regeneration of descending pathways and minimal changes in hindlimb muscle properties. Thus, recovery must be due to plasticity in spinal networks, with the precise loci and mechanisms hardly known. The application of various drugs (e.g., clonidine, serotonin, dopamine, N-methyld-aspartic acid, bicuculline, strychnine) may improve the spinal cats ability to walk [20,83,316]. Instigated by the animal experiments, similar combinations of locomotor training, drug application and functional electrical stimulation have been tried in humans with stroke or spinal cord injury [103]. Daily locomotor training on a treadmill of incomplete and complete paraplegics aided by partial weight support increased ankle extensor activity during the stance phase, while the inappropriately enhanced tibialis anterior activity during swing decreased. The increase in extensor activity was probably due to load-receptor stimulation during partial weight bearing and went beyond any spontaneous recovery without training. A number of pharmacological and other treatments have been used to support functional recovery. The mechanisms underlying training-induced plasticity are not well understood and need further research [20,74,75,83,316]. 12.3. Plasticity of the stance support system The stance support system should be calibrated just right to provide proper support without jeopardizing stability. This requires plastic processes that adapt the system to prevailing circumstances. When in the cat hindleg the nerves to synergist muscles (lateral gastrocnemius, soleus, plantaris) of the medial gastrocnemius muscle were cut, the ankle extensors initially yielded during the locomotor stance phase. Stimulation of the medial gastrocnemius nerve became progressively more effective in prolonging the extensor burst duration [205]. Moreover, such partial denervation entailed that, in walking cats, the magnitude of medial gastrocnemius bursts during the stance phase increased progressively so as to compensate for the neurectomyinduced loss of extensor thrust. The early medial gastrocnemius electromyographic activity, generated before paw ground contact by central drive, increased gradually over a one-week period. The mid-stance portion of the medial gastrocnemius electromyographic burst, driven centrally and by sensory feedback, increased rapidly, within the rst few days. It has been suggested that this early increase of the mid-stance activity was due to an increase in reex gain from medial gastrocnemius afferents to medial gastrocnemius -motoneurons, possibly via a facilitation of the disynaptic pathway [205,284]. Proprioceptive signals are important, as potential error signals, for spinal learning processes. For example, the recovery of locomotion after ankle extensor nerve section (reported above) was abolished after pyridoxine-induced loss of large-diameter afferents, which by itself initially caused severely dysfunctional locomotion, which recovered over a few months, however. This is consistent with the hypothesis that proprioceptive feedback from group I afferents be necessary for functional recovery [286].

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In experiments designed to check for changes in stretch reex gain after partial ankle extensor denervation (above), the increase in medial gastrocnemius activity before paw ground contact was accompanied by a proportionate increase in reex bursts in response to sudden extensor stretches elicited by pegs popping up. This has been interpreted as indicating an adaptive increase in the centrally generated pre-contact electromyographic activity, which secondarily accounts for increases in stretch responses, without any reex gain changes [131]. The differences in interpretation of results from the two series of experiments may be due to differences in methods and conditions. In any case, there must be spinal mechanisms that can detect and compensate for decits arising peripherally [205]. Gastrocnemius muscles are usually active only during the stance phase, although, as biarticular muscles, they also produce knee exor torques. But when other knee exor muscles are partially denervated, the gastrocnemius muscles are recruited well into the swing phase, probably in order to compensate for the decient knee exor torque [359]. Exactly how the plastic processes required for the proper calibration of the stance support system are regulated is not yet well understood [281]. It is very likely that several processes contribute to the adaptations of centrally generated drives and potentially reex gains. In the following, a novel model for one such mechanism is proposed. 12.4. A hypothesis on the role of recurrent inhibition in learning Here we will discuss the possibility that recurrent inhibition, beyond its online function, might provide a mechanism involved in regulating, calibrating and adapting the patterns and quantitative characteristics of excitatory reex inputs to -motoneurons during the stance phase. It is hypothesized that recurrent inhibition does so by inuencing the degree of retrograde invasion of the -motoneuron dendritic trees by back-propagating action potentials, which are assumed to serve as a postsynaptic signal to be correlated with presynaptic signals for Hebbian synaptic plasticity (Windhorst and Hamm, in preparation). This necessitates a brief digression into back-propagating action potentials, their effects in synaptic plasticity and their modulation. 12.4.1. Back-propagating action potentials Spinal -motoneurons are among the CNS neurons whose action potentials originate close to the origin of the centrifugal axon and then not only travel down the efferent axon, but also back-propagate into the dendritic tree. These back-propagating action potentials are supported by active, tetrodotoxin-sensitive, voltage-dependent sodium channels and possibly calcium channels, and decrease in amplitude but increase in width, the further they travel into the tree. The extent of this decremental backprogagation varies widely between different types of central neurons, different specimens of the same type, and possibly different dendritic branches of individual cells. It also depends on cell morphology and densities of dendritic ion channel as well as modulatory inuences, as provided by excitatory and inhibitory

inputs as well as neuromodulators. On average, the extent and decrement of action potential back-propagation appear to be of intermediate degree in -motoneurons [206,358,377]. Several functions have been proposed for back-propagating action potentials, among which are [377]: Short-term changes in synaptic efcacy due to the backpropagating action potentials drastic effects on membrane potential and voltage- and time-dependent dendritic ion channels, whereby the properties of synaptic conductances are changed. Long-term changes in synaptic efcacy. Back-propagation is a term used in neural network theory for an algorithm of unsupervised learning. The strengths of synaptic inputs on network neurons are changed according to the output signals, which back-propagate into the network. This algorithm has prompted the idea that back-propagating action potentials could do essentially the same in natural neurons [60,358,377]. This idea is in accord with that proposed before the neural-network rave by Hebb [142] who envisaged that learning in the CNS occurred by changes in synaptic efcacy such that synapses would be strengthened whenever pre- and postsynaptic neurons red simultaneously, and vice versa. The precise timing of presynaptic inputs and postsynaptic spikes determines whether excitatory synaptic inputs are strengthened or weakened. The long-term increases often depend on increased calcium inux, which may elicit a cascade of metabolic events leading to changes in synaptic efcacy. The rises in intra-dendritic calcium concentrations occur following (i) activation of voltage-dependent calcium channels due to the back-propagating action potential, (ii) activation of postsynaptic N-methyl-d-aspartate channels during depolarization [206,358,377]. Thus, nearly coincident pre- and postsynaptic activity and consequent intra-dendritic calcium increases would be expected to strengthen excitatory synapses. 12.4.2. Inuence of inhibition on back-propagating action potentials The extent of action potential back-propagation into the dendritic tree is not invariant, but depends on several variables, such as interactions between synaptic inputs and postsynaptic activity and modulatory factors. Appropriately timed excitatory inputs to distal dendrites may enhance action potential back-propagation, and inhibitory (e.g., GABAergic) inputs suppress it [358,377]. Inhibition and the underlying changes in local membrane potential and conductance are of special concern here. Locally operating inhibitory inputs may control the routes of action potential propagation through the dendritic tree and thereby the action of action potentials on other synaptic inputs. This complements an age-old idea about the strategic position of inhibitory inputs. Depending on where in the soma-dendritic tree the inhibition operates, it may differentially inuence the propagation of excitatory synaptic currents to the action potential-generating site. Inhibition at the soma would globally shunt excitation originating in vast spaces of the dendritic tree, while local inhibition in the dendrites would

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counteract excitation originating peripherally to the site of inhibition. The converse may now hold for back-propagating action potentials. Synaptic inhibition acting at the soma may prevent or attenuate back-propagating action potentials and, hence, quench their effects on synaptic inputs widely distributed in the dendritic tree, while local dendritic inhibition may have subtle and selective local effects. Recurrent inhibition is among the types of inhibition inuencing action potential back-propagation. In order to exert its proposed effects, however, several corollaries must be met. 12.4.3. Corollaries (i) Since most of the excitatory inputs to be modied arrive in the -motoneuron dendritic tree, recurrent inhibition should also act dendritically, in distinction to other inhibitory inputs, that is, the Renshaw cell synapses should be located on dendrites. This is the case [41,109,227]. (ii) Since, via muscle spindles, -motoneurons contribute to the afferent inputs to -motoneurons in an ordered and adjustable way, they too should be subject to recurrent inhibition. This is the case (Section 4.3.2). (iii) Since the connections of group Ia muscle spindle afferents to reciprocal Ia inhibitory interneurons should obey an ordered and adjustable spatial pattern complementing that of homonymous monosynaptic Iamotoneuron connections, reciprocal Ia inhibitory interneurons should also be subject to recurrent inhibition. This is the case (Section 4.3.2). (iv) All neuronal elements involved in the above adaptation processes (sensory and potentially other inputs, -motoneurons, -motoneurons, reciprocal Ia inhibitory interneurons, and Renshaw cells) should be active concurrently during the relevant stance phase. This is the case (Section 5). 12.4.4. Operation of the model after neurectomy The sheer complexity of the system outlined above makes it difcult to envisage exactly how the suggested mechanism works under normal circumstances. A drastic pathological case may give an idea. As described in Section 12.3, severance of cat hindlimb nerves to synergist muscles of the medial gastrocnemius muscle causes, in the acute phase, biomechanical changes (ankle yielding and extensive extensor muscle stretch during the stance phase) accompanied by a lack of proprioceptive support from synergists to the medial gastrocnemius muscle [205]. This lack of proprioceptive support would reduce the excitatory input to medial gastrocnemius and synergistic -motoneurons, which in turn would reduce their recruitment and ring rates, which in turn would reduce recurrent inhibition, which nally would reduce the inhibition of action potential back-propagation. Consequently, action potential back-propagation would be promoted, thereby enhancing the potentiation of excitatory inputs to compensate for the lack of such inputs to ankle extensors. Another mechanism might contribute to the depression of recurrent inhibition under these conditions. The initial ankle yielding after neurectomy would activate ankle extensor muscle spin-

dle group II afferents, which have been suggested to inhibit homonymous Renshaw cells [391]. Evidently, the mechanism described above is based on the balance of interactions within a complex network. Under less dramatic circumstances, the balancing interactions must be expected to be subtler, which are difcult to illustrate, though, except perhaps by computer simulations. 13. Transformations revisited The spinal cord circuitry is in fact capable of solving some of the most complex problems in motor control and, in that sense, spinal mechanisms are much more sophisticated than many neuroscientists give them credit for ([295], p. 269). Specically, the vertebrate spinal cord is able to solve, at least to some degree, (i) the degrees-of-freedom problem, (ii) the problem of complex spatial sensory-motor transformations, and (iii) the inverse dynamics problem [295]. While, at a global level, this assertion is veried by the very existence of complex motor acts performed by spinalized animals, the precise manner in which the spinal cord implements these acts by neurons and neuronal networks is anything but clearand maybe principally difcult to understand. This is particularly so for the latter two functions listed above, namely spatial sensory-motor transformations and the inverse dynamics problem, which thus need reconsideration. 13.1. Spatial representations and transformations Based on sensory feedback, spinal cord networks establish spatial representations of the peripheral biomechanical apparatus (body schema) and perform transformations between different representations, sensory and motor, kinematic and kinetic. The questions as to which networks perform these tasks, and how, have been largely neglected in spinal cord neurophysiology. Some ideas may be gleaned from a brief comparison with cortical mechanisms. First, there are different types of spatial representations, one being related to in part topographically organized maps. The CNS in general carries motor maps and maps derived from different sensory modalities, e.g., visual, auditory, proprioceptive. Similarly, the spinal cord carries motor maps and maps based on different modalities, cutaneous, proprioceptive, etc. For goaloriented movements, these different maps must be calibrated and put in register with respect to each other, for body part, limb and target localizations. Target-oriented movements require the determination of target location with respect to the moving body part, both in voluntary arm reaching as well as wiping and scratch reexes. This also involves an estimate of the initial state of the motor apparatus. While these statements may appear trivial (they make sense), the processes by which the requirements are implemented at network and cellular levels are anything but trivial. Secondly, the sensory and motor spatial representations are coded in different frames of reference. For example, at cortical level, vision is coded in retinal or eye-centered coordinates, sound in head-centered coordinates, and touch and propriocep-

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tion in (different) body-centered coordinates. There are opposing hypotheses as to how, in the posterior parietal cortex and premotor cortex, signals are represented in coordinate systems. One hypothesis posits that different cortical areas are specialized in coding space in different frames of reference [7,22,124]. To relate the different spaces to each other and put them in register, coordinate transformations must be performed. The above view implicitly suggests that these coordinate transformations occur in a sequential way in successive areas. This view has been contested by an alternative hypothesis emphasizing the hybrid, task-dependent and probabilistic nature of independently coexisting reference frames. On this view, the frame of reference used to specify the target of an arm reach depends on task demands, the available sensory information, the structure of the visual space and on cognitive context [21]. This view emphasizes the distributed neural-network structure of the cortex, in which individual neurons cannot be ascribed circumscribed identiable functions. If the spinal cord performs transformations according to the same scheme, there must be neuronal networks with individual neurons not having individual functions. Hence, the operation of the involved interneurons cannot be made sense of. At spinal level, this discussion is still ahead of us (see below). Thirdly, in any case, what is required is that signals from various sensory sources converge, thus creating a multi-modal space, and that, on the motor output side, stimulus locations must be transformed into body-centered coordinates of muscles. At cortical level, multi-modal convergence is particularly prominent in the posterior parietal cortex [22]. Extensive convergence of multi-modal sensory afferents and descending systems is also prevalent in spinal neurons. It seems tempting to assume that, in the spinal cord, space is coded along principles similar to those operating at cortical level. In this regard, little is known about the involvement of interneurons, but some data are available for cells of origin of the dorsal spinocerebellar tract in Clarkes column. 13.2. Coding of kinematics and kinetics in dorsal spinocerebellar tract cells Dorsal spinocerebellar tract neurons in cats receive monosynaptic connections from muscle spindle group Ia afferents from the hindlimb and lower trunk. The same dorsal spinocerebellar tract cells may also receive monosynaptic inputs from spindle group II bers. Distinct sub-groups of dorsal spinocerebellar tract cells are monosynaptically excited by group Ib afferents from Golgi tendon organs. The effects from both types of group I afferents are powerful, as suggested by large presynaptic boutons and large excitatory postsynaptic potentials. Joint afferents project to still other groups of dorsal spinocerebellar tract cells. In addition, however, there are many polysynaptic connections with convergent inputs from various loci and modalities, making Clarkes column and other dorsal spinocerebellar tract cell groups a complex processing and integrating network [32,36,163,374]. Dorsal spinocerebellar tract cells also receive cutaneous nociceptive inputs [330]. Thus, dorsal spinocerebellar tract neurons show multi-modal convergence with some fractionation as also seen in spinal neurons (Section 8).

The discharge of dorsal spinocerebellar tract neurons during passive movements varies broadly with limb length and orientation, i.e., is related to global kinematic variables. Moreover, many dorsal spinocerebellar tract cells respond to the direction of movement from one position to another. Thus, position and movement variables are coded simultaneously, but not independently. During foot movements, various response components to particular kinematic limb variables are distributed across the dorsal spinocerebellar tract cell population. The two most inuential ones correlate well and independently with limb axis length and orientation. These major response components may be integrated from signals arising from muscle, joint and cutaneous receptors. Even if these bear a local signature, they are also inuenced by global limb conguration, due to the coupling of different joints. Thus, weighted inputs from receptors primarily modulated by changes in hip and knee angles could lead to the preferential representation in dorsal spinocerebellar tract cell discharge of limb orientation. Similarly, weighted inputs from receptors modulated by changes in knee and ankle angles would favor the representation of limb length. The moderate velocity sensitivity of these response components appears to reect that of muscle spindles. There are, however, higher-order response components that are unrelated to limb orientation or length and instead appear to reect response dynamics. Furthermore, in a proportion of dorsal spinocerebellar tract cells, muscle force may alter the sensitivity to limb position uniformly across the entire workspace, implying the representation of a kinetic variable along with kinematic variables [32]. Specically, dorsal spinocerebellar tract cell responses to active locomotion in decerebrate cats differ from those in passive limb movements. The differences have been attributed to an increased relative prominence of specic response components occurring during the stance phase of active stepping. Thus, under these active conditions, dorsal spinocerebellar tract neurons may encode two global variables of limb mechanics, namely limb axis orientation and limb loading, the latter being closely linked with limb-axis length. Hence, global coding in dorsal spinocerebellar tract cells appears to be in a hybrid kinematic/kinetic framework [33]. In summary, populations of dorsal spinocerebellar tract cells perform complex computations based on the convergence of multi-model inputs and delivering global kinematic signals with some admixture of dynamic variables. While the dorsal spinocerebellar tract cells send their signals to the cerebellum, they may still serve as a model for transformations occurring at spinal segmental level in interneurons. It is about time to start investigating spinal interneurons in the way dorsal spinocerebellar tract neurons have been studied [32]. 13.3. Kinematickinetic mixtures The preceding discussion suggests that spinal neuronal populations may well represent and transform kinematic variables and thus kindles the hope that they might cope with the required kinetic transformations (Section 2) as well. As a matter of fact, they can do that, as evidenced by all pretty well-behaved motor acts of spinalized preparations. How exactly, by what means,

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kinetic transformations are implemented at spinal level is a question difcult to answer, however. One reason is that it is not quite certain that kinetics are represented and dealt with independently of kinematics, neither at higher organizational levels nor at lower spinal level. A brief digression to supraspinal levels may serve to make the point and unveil some similarities to coding in dorsal spinocerebellar tract neurons. This is also justied by recent results indicating similarities (besides differences) between discharge patterns of cortical neurons and spinal cord interneurons during primate voluntary hand movements [98]. Cell discharge in the primary motor cortex (M1), which is close to motor output, particularly in primates (and rats: [52], is related to both kinematic and dynamic variables. The primary motor cortex cell ring is in part related to the time course and strength of muscle activation (dynamic variable in an intrinsic coordinate system). The summed discharge of a population of cortico-motoneuronal cells known to excite a muscle (group) is strongly correlated with isometric muscle force plus its derivative [96,156,173], and cell discharge in caudal primary motor cortex co-varies with the direction of force, which may change in the course of a movement [335]. On the other hand, the direction of the hand trajectory (in an extrinsic coordinate frame) during reaching movements appears to be encoded in the aggregate discharge of populations of cortical (and other, e.g., basal ganglia and cerebellar) neurons, each of which is broadly tuned to its individual preferred direction [115,168,169] (for critique, see ref. [96]). Moreover, discharge components related to scalar variables, such as speed, amplitude and accuracy, may unfold sequentially throughout a motor task [169]. These directionally tuned cells are also responsive to static loads, however, such that they can compensate for external forces and encode the net force needed to move in the correct direction. Thus, some researchers have tried to take an intermediary stand in arguing that cortical discharge is tuned to both movement and load direction, the representations of these variables gradually shifting across the motor and premotor cortices [169,173,335]. Furthermore, even in primary motor cortex, the ring of some cells is more closely correlated with joint position or preparatory set, and these relations can change depending on the motor task studied, such that the same cell may code different parameters under different response conditions [96,335]. Moreover, cell discharge is inuenced by starting position and arm posture, which probably reects the inuence of proprioceptive signals, as well as by eye position, visual target position and selective attention [169]. Often neglected are those many cells whose discharge patterns show complex relations to movement parameters or are unmodulated during movement and yet contribute to muscle activations [52,96]. Thus, motor cortex and even individual neurons carry various, mixed and exible representations of movement variables. It has been suggested that primary motor cortex, particularly its caudal part, might be involved in transforming kinematic into kinetic variables [52,174,335]. Neural discharge patterns as described above are not only found in the primary motor cortex, but occur widely distributed in various motor-related structures, including cells in the dorsalroot ganglion [96]. Since various supraspinal structures project to spinal neurons (Section 5.1.6), it is not surprising that the

latter exhibit discharge patterns that in part resemble those of supraspinal neurons, with differences also being apparent. In particular, in monkeys, many cervical pre-motor interneurons (with actions on single muscles or muscle groups) show preparatory activity prior to movement onset, relations to muscle force and spatial tuning to force direction. Some interneurons behave as expected for reciprocal Ia inhibitory interneurons or Renshaw cells. In contrast to cortico-motoneuronal cells, afferent pre-motor bers and motor units, three quarters of the pre-motor interneurons are bi-directional in being active in opposite movement directions as well as at rest, thus resembling rubral neurons. About half of the interneurons with task-modulated activity have a preferred direction of action, thus resembling motor cortical cells, whose spatial tuning is sharper, however [98]. It appears appropriate to conceive of encoding schemes, which involve the discharge patterns of populations of neurons whose ensemble discharge encodes global rather than single, articially isolated mechanical variables. While such schemes may be more difcult to envisage, they on the other hand appear more natural because, rstly, complex motor acts can rarely be described in terms of selected Newtonian variables such as force and position and, secondly, single motor cortical cells, as other neurons along the neuraxis, usually receive a complex mixture of sensory inputs, so that their discharge can hardly be imagined to be invariably related to an individual mechanical variable singled out by the experimenter during an experiment in which the monkey is trained to perform a predened task [96]. This leads to a more general consideration. Provided that proprioceptive afferents contribute to the control of kinematic and dynamic variables, the latters independent control might at rst glimpse appear to be supported by the classical functional interpretation of large-diameter muscle afferents. Muscle spindle group II afferents are usually regarded as muscle length receptors, group Ia afferents as length plus velocity receptors and Golgi tendon organs as force receptors [299]. This ts well with a Newtonian description of motor control in terms of variables such as position, velocity, force or mechanical impedance, but is not the only possible one and does not guarantee that the nervous system operates in these terms [278] (for more extensive discussion, see ref. [387]). First, at muscle level, length and force are inextricably interwoven, nonlinearly interacting with each other, and this is reected in muscle afferent discharge. Because muscle spindles lie in parallel to muscle bers in series with elastic elements, muscle spindles devoid of fusimotor input would reduce their ring rate, in a force-related manner, during isometric contraction of their parent muscle (or part thereof). This is precisely the reason why concomitant -activity is needed to keep them ring, with this -determined component of spindle activity often corrupting any unambiguous relation of the afferent signals to length or force (Section 5.1.5). The spindles in passive antagonist muscles may here help preserve a clearer relation to length and/or velocity [299]. Furthermore, as mentioned throughout this review, there are many instances of convergence of subsets of muscle spindle and Golgi tendon organ afferents onto various sets of interneurons, creating mixed representations. So the question remains open as to how independent kinematic and kinetic control might be achieved. In any case, the spinal cord must be

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able to handle both kinematic and kinetic aspects because it can organize fairly normal-looking behaviors. 14. Final comments Can sense be made of spinal interneuron circuits? [247]. Yes and no, depending on what is meant by making sense. Most investigators would probably agree that making sense is closely related to understanding the function or role of the nervous system or its parts in normal animal behaviors. Of course, sense and understanding depend, besides on our mental capacities, investigative means and concepts employed to penetrate reality, on the level of organization: whole organism, macroscopic neural structure, network, neuron, ion channels, etc. For example, at the organismic level, the frogs wiping reex, or the scratch reex of turtle, cat or dog, or the paw-shake response, or the withdrawal reex [332], aim at removing an irritant stimulus from the body surface, which makes immediate functional sense, in the framework of an individuals drive for survival. It would be more difcult to assign specic functions to existing neuronal circuits, although, of course, there must be sensory receptors, motoneurons, possibly interneurons, and appropriately wired network connections linking these classes. And, of course, there must be some basic networks, such as propriospinal systems coordinating forelimb and hindlimb motoneuron activities and bilateral connections coordinating motoneuron activities on both sides of the spinal cord [42,72,166,185]. Even these networks are emerging as complicated, however, not surprisingly, since individual limbs can walk fairly independently of others, in exible combinations, as demonstrated amply by many slit-belt treadmill experiments. Probably one of the most sensible and easily understandable networks is reciprocal Ia inhibition between antagonist muscles at major limb joints involved in locomotion. This prompts the question as to the function of muscle spindle group Ia afferents themselves. Strangely, this question appears more difcult to answer. The phylogenetically ancient and seemingly simple monosynaptic reex that has been interpreted as a postural negative feedback (that) helps to maintain a given position ([58], p. 199), appears to play a disappointingly small role in the maintenance of upright quiet stance in cats and humans. In classical ballet dancers, the Achilles and patellar tendon tap reexes can be reduced or get lost [118,189], or the H-reex is suppressed while being increased in trained athletes [273], attesting to its modiability, but also its disposability in some cases. Instead, spindle group II afferents have conquered the front stage. But central actions of these afferents, too, like those from group Ia afferents, are subject to large modulating inuences from various sources. Sensory-motor transformations may be principally uninterpretable at the level of individual neurons. If the spinal cord employs methods similar to those apparently used by the cerebral cortex, individual neurons may not have specic recognizable functions. The interface between sensory afferents and motoneurons may consist of a core of multi-functional and multi-modal hidden units with fuzzy borders. However, the peripheral interface between motoneurons and sensory afferents also takes part in computing spatial transformations, possibly being more

orderly and thus somewhat easier to interpret, although presentday experimental techniques do not yet sufce to yield a complete insight into its workings during natural behaviors. Over the past several decades, therefore, there has been growing scepticism, even frustration, as to our ability to understand neuronal networks. This scepticism has also grown from the experience with articial neural networks designed to model real neuronal networks. Engineers use neural networks to control systems too complex for conventional engineering solutions. To examine the behavior of individual hidden units would defeat the purpose of this approach because it would be largely uninterpretable. Yet neurophysiologists spend their careers doing just that! Hidden units contain bits and scraps of signals that yield only arcane hints about network function and no information about how its individual units process signals. Most literature on single-unit recordings attests to this grim fact ([310], p. 644; see also [96]). This is no argument for viewing the sensory-motor control system as a uniformly diffuse, disorderly, unstructured network. It had better be envisaged as a hybrid system containing some elements with reasonably well identiable sub-functions and other elements defying such descriptions. A simple analogy would be the vestibulo-ocular reex and other oculomotor systems that incorporate an internal model, i.e., the neural integrator [13,262,264,310]. The neural integrator has been modelled as a learning neural network [13,310]. While the functions of individual neurons may not be precisely denable, there may still be a gross differentiation in that subsets of neurons assume understandable roles. For example, inhibitory neurons tend to project contralaterally, thus forming an inhibitory commissure coordinating conjunct eye movements [13]. Analogously, in the spinal cord, there may be some functional specialization, for example for commissural interneurons, which are bound to exist. Other interneurons, however, such as those involved in complex kinematic and kinetic transformations, may elude our quest for making sense. This somewhat pessimistic note should not prevent us from further delving into spinal neuronal networks and their potential functions. Advances may, however, require the development of new methods, for example improved chronic recording techniques during natural motor behaviors, as well as genetic and embryological techniques [154]. Conict of interest None. Acknowledgements I am very grateful for encouraging comments and helpful suggestions to Drs. A. Moschovakis, T.R. Nichols, R.E. Poppele, S. Roatta, M. Schieppati, and D.G. Stuart. References
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