INTRODUCTION TO Nervous System

By Prof. Dr. Abdul Majid MBBS, M.Phil, FCPS

Nervous System
It is the most excitable tissue of the body. It receives information from external or internal environment. Integrates this information. Controls rapid activities of the body like contraction of muscles and secretion from glands. It is also responsible for higher functions as consciousness, memory & creativity.

Composition
1. Neurons or nerve cells which can generate and propagate nerve signals >100 billion. 2. Neuroglial cells which can not generate and propagate nerve impulses 10-50 times as many as neurons.

Structure of a Large Neuron in the Brain

Functional Types of Neurons

1. Sensory or afferent neurons. 2. Motor or efferent neurons. 3. Inter neurons or connecting neurons .

Neuroglial Cells in the Brain

Astrocytes
Astrocytes are found throughout the brain & are of two types. 1) Fibrous Astrocytes: The contain many intermediate filaments, & are found primarily in the white matter. 2) Protoplasmic Astrocytes: The have granular cytoplasm & are found in gray matter

Functions of Astrocytes:
Both types of astrocytes send process to the blood vessels, where they induce capillaries to form tight junctions that form the blood brain barrier. They also send process that envelop the synapses and surface of nerve cells.

 They produce substances that are trophic to neurons. They help maintain the appropriate concentration of ions and neurotransmitters by taking up K+ ions and neurotransmitter glutamate & (GABA).

Anatomical Division of NS

NS
CNS
Brain Spinal cord

PNS
Nerve & Ganglia 12 pairs of cranial nerves 31 pairs of spinal nerves

PNS

Sensory (Afferent)

Motor (Efferent)

Somatic

Autonomic Splanchanic or visceral

Somatic To skeletal muscles for voluntary Control of movements

Autonomic To viscera or glands

ANS

Sympathetic Thoraco lumbar outflow (T1- L2 or L3)

Prepares the body to deal with immediate t Threats to internal environment of the body It provides flight & fight responses

Parasympathetic Cranio sacral outflow (3rd, 7th, 9th, 10th ) cranial nerves, Sacral nerves include S2, S3
Coordinates body's normal resting activities, hence Called rest & repair division

Cranial Nerves
1. 2. 3. 4. 5. 6. Olfactory Optic Occulomotor Trochlear Trigeminal Abducent 7. Facial 8. Vestibulo-cochlear 9. Glossopharyngeal 10. Vagus 11. Accessory 12. hypoglossal

 Functionally 1, 2, 8 are purely sensory nerves 3, 4, 6, 11, 12 are purely motor nerves 5, 7, 9, 10 are mixed nerves.

Physiological Division of NS
(General design or organization of NS) There are three divisions: 1. Sensory input division which includes sensory receptors organs and or sensory nerves. 2. Central nervous system or integrative division. 3. Motor output division which includes motor nerve supply to effectors.

The Sensory Input Division

The sensory receptors detect state of the body or state of the surroundings. For instance, receptors in the skin detect sensations of touch, pressure, pain & temperature. Eyes detect light while ears detect sound. Sensory receptors are also called transducers because they convert different forms of energy (stimuli) into action potentials.

Importance of sensory division: Most activities of the NS are initiated by sensory experiences detected by sensory receptors or organs. The sensory experience can either cause an immediate reaction of the body or Memory of sensory experiences can be stored in the brain for minutes, hours, weeks or years to determine bodily reaction at some future date.

Sensory sensations may be: 1. Somatic coming from entire body surface and from some deep tissues. 2. Autonomic or visceral sensation coming from internal organs of the body or glands.

Somatic Sensation from Skin & Deep Tissues

Sensory areas of CNS

When somatic sensations travel through peripheral nerves to the CNS they are conducted to multiple sensory areas. All levels of spinal cord. Reticular substance of brain stem. Cerebellum. Thalamus. Cerebral cortex.

1. 2. 3. 4. 5.

CNS or Integrative Portion

It is composed of brain and spinal cord.

Brain can:
1. 2. 3. 4. Store information. Generate thoughts. Create ambitions. Determine reaction of the body in response to sensory sensation.

Spinal cord can:

1. Conduct impulses to & from the brain. 2. Generate reflex actions.

CONT:
One of the most important functions of the CNS is to process incoming information in such a way that appropriate mental & motor responses occur. More than 99% of all sensory information is discarded by the brain as irrelevant & unimportant.

 When important sensory information excites the mind it is immediately channeled into proper integrative and motor regions of the brain to cause desired response, this channeling and processing of information is called integrative function of NS. Thus, if a person places a hand on a hot stove, the desired instantaneous response is to lift the hand, associated responses are moving of the entire body away from the stove and even perhaps shouting with pain.

Role of Synapses in processing information

The synapse is the junctional point b/w two neurons. 1. The synapses determine the directions in which the nerve signals will spread in the NS. 2. Some synapses transmit signals from one neuron to the next with ease, where as others, transmit signals only with difficulty.

3. Facilitatory and inhibitory signals from other areas in the NS can control synaptic transmission, sometimes opening the synapses for transmission and at other times closing them. 4. Some post synaptic neurons respond with large numbers of output impulses & other respond with only a few. 5. Thus the synapses perform a selective action, often blocking weak signals while allowing strong signals to pass.

6. At other times selecting & amplifying certain weak signals. 7. Often channeling these signals in many directions rather than in one direction. 8. They store information called memory function.

Storage of memory:
1.Cerebral cortex. 2.In basal regions of brain. 3.Spinal cord. Mechanism: Each time certain type of information passes through sequences of synapses, these synapses become capable of transmitting the same type of signal the next time, a process called facilitation.

After the sensory signals have passed a large number of times, the synapses become so facilitated that signals generated with in the brain may be perceived as if original sensation is there.

Summary:
After processing sensory information it is channeled to: 1. Certain storage areas for future response & also for thinking process. 2. Certain integration areas. 3. Certain motor areas for immediate response.

Motor Division of Nervous System

It controls: contraction of appropriate skeletal muscles. Contraction of smooth muscles throughout the body. Secretion of chemicals from both exocrine & endocrine glands. These activities are collectively called motor functions of NS, & muscles & glands are called effectors.

Skeletal Motor Nerve Axis of NS

Autonomic motor axis:

Parallel to somatic motor axis is the autonomic motor axis which controls activities of smooth muscles & glands. Skeletal muscles can be controlled from many levels of CNS. Spinal cord. Reticular substance of brain stem. Basal ganglia. Cerebellum. Motor cortex.

1. 2. 3. 4. 5.

Major Levels of CNS Functions

1. Spinal cord level. 2. Lower brain or subcortical level. 3. Higher brain level or cortical level.

Cont:
Spinal cord level: Conducts sensory and motor impulses to and from brain. In a spinal animal neuronal circuits within spinal cord can produce. Walking movements. Reflexes that withdraw portions of the body from painful objects. Reflexes that stiffen the legs to support the body against gravity.

Cont:
Reflexes that control local blood vessels. Reflexes that control urinary bladder excretion. Gastrointestinal movements. 3. Higher centers send command signals to spinal cord centers and from there impulses pass to effectors.

Lower Brain or Subcortical Level

Many of the subconscious activities of the body are controlled by areas of the lower brain like medulla, pons, mesencephlon, thalamus, hypothalamus, cerebellum and basal ganglia. These activities includes: 1. Subconscious control of arterial blood pressure and respiration in the medulla and pons. 2. Control of equilibrium is the combined function of older portions of cerebellum & reticular formation of brain stem.

Cont:
3. Feeding reflexes like salivation in response to taste of food and the licking of the lips are controlled by areas in the medulla, pons, mesencephlon, amygdala and hypothalamus. 4. Many emotional patterns such as anger, excitement, sexual response, reaction to pain and reaction to pleasure can occur in animals after destruction of cerebral cortex. 5. Concerned with wakefulness of cerebral cortex.

Higher Brain or Cortical Level

1. Large store house of memory. 2. It nerve functions alone but always in association with lower brain centers although without cerebral cortex the functions of lower brain centers are often imprecise. 3. It is essential for most of our thought processes.

Comparison of NS With the Computer

In case of simple computers there are input circuits which are comparable to sensory portions of NS. Output circuits are comparable to motor portions of NS. In more complex computers there is central processing unit that determines the sequence of all operations as in the brain there is sequence of thoughts or motor actions.

CNS Synapses
In the CNS information is transmitted in the form of nerve actions potentials which passes through successive neurons. In addition each impulse. 1. May be blocked in its transmission from one neuron to the next. 2. May be change from a single impulse into repetitive impulses or 3. May be integrated with impulses from other neurons to cause highly intricate patterns of impulses in successive neurons.

Physiological Classification of Synapses

Chemical Synapses: 1. Transmission occurs by releasing neurotransmitter. 2. Unidirectional transmission. 3. Gap junctions absent. 4. Width of synaptic cleft 200-300 A. 5. In human CNS 99%. Electrical Synapses 1. Transmission occurs by direct electrical spread. 2. Bidirectional transmission. 3. Gap junctions present. 4. Width of synaptic cleft 20-30 A. 5. In human CNS 01%.

Mechanism of Action of a Neurotransmitter

Action of a neurotransmitter released depends upon the receptor protein (excitatory or inhibitory) present on the postsynaptic membrane. 1. A binding component that protrudes outwards from the membrane into synaptic cleft-here it binds the neurotransmitter coming from the presynaptic terminal.

Cont:
2. An ionophore component that passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron. The ionophore in turn is one of the two types: An ion channel that allows passage of specific types of ions through the membrane or A second messenger activator that is not an ion channel but instead a molecule that protrudes into the cell cytoplasm & activates one or more substances inside the postsynaptic neurons.

Cont:
These substance serve as second messengers to increase or decrease specific cellular functions. The ion channels in the postsynaptic membrane are of two types: 1. Cation channels that most often allow sodium ions to pass when opened, but some times allow potassium and / or calcium ions as well and 2. Anion channels that allow mainly chloride ions to pass but also minute quantities of other anions.

Cont:
When cation channels open and allow positively charged sodium ions to enter this will excite the neuron and the neurotransmitter which causes such change is called excitatory neurotransmitter. Conversely when a neurotransmitter causes opening of anion channels, the negatively charged ions enter the cell and cause its inhibition. Such a neurotransmitter is called inhibitory neurotransmitter.

Types of Neurotransmitter
1. Small molecule, rapidly acting transmitter. Class - I Acetylcholine Class - II The Amines (Norepinephrine, epinephrine, dopamine, serotonin, histamine) Class - III Amino Acids (GABA, glycine, glutamate, aspartate) Class - IV Nitric oxide (NO)

Cont:
2. I. Neuropeptide, slowly acting transmitters or growth factors. Hypothalamic releasing hormones: Thyrotropin releasing hormone Luteinizing hormone releasing hormone Somatostain (growth hormone inhibitory factor) Pituitary peptides: ACTH Beta endorphin Alpha melanocyte stimulating hormone Prolactin LH TSH GH Vasopressin Oxytocin

II.

Cont:
III. Peptides that act on gut & brain: Leucine enkephalin Methionine enkephalin Substance P Gastrin Cholecystokinin VIP Nerve growth factor Neurotensin Insulin Glucagon Brain derived neurotropic factor

Cont:
IV. From other tissues: Angiotensin II Bradykinin Carnosine Sleep peptides Calcitonin

Distribution of 03 Ions Across Neuronal Somal Membrane

Electrical Events During Neural Excitation

Resting membrane potential of the neural soma is about 65mv. This is some what less negative than the 90mv found in large peripheral nerve fibers and in skeletal muscle fibers: the lower voltage is important because it allows both positive and negative control of the degree of excitability of the neuron.

Cont:
Concentration differences of ions across the neuronal somal membrane. Sodium ions - Sodium pump Potassium ions - potassium pump Chloride ions - weak chloride pump and negative potential inside the soma. (-65mv) A potential that exactly opposes movement of an ion is called Nernst potential for that ion:

Cont:
The equation for this is following: EMF (mV) = +- 61 X Log (concentration inside / concentration outside) Where EMF is the Nernst potential in mV on inside of the membrane. The potential will be negative(-) for positive ions and positive (+) for negative ions. Nernst potential for sodium ions will be +61mV Nernst potential for potassium ions will be -86mV. Nernst potential for chloride ions will be -70mV.

Cont:
Effect of synaptic excitation on postsynaptic membrane excitatory postsynaptic potential (EPSP). Figure A shows resting membrane potential inside the soma. (-65mV) Figure B shows hypo polarization due to influx of sodium ions and rise in resting membrane potential from -65 to -45mV. Figure C shows hyperpolarization due to influx of chloride ions and or out flux of potassium ions.

Cont:
The threshold level for excitation is 45mV. Only few presynaptic nerve terminals will not be able to excite the postsynaptic neurons, for this at least 4080 presynaptic nerve terminals are required. When these many presynaptic terminals send impulses to postsynaptic membrane at the same time or in rapid succession then summation occurs and action potential is generated in the initial segment which then travels along the axon.

Cont:
Action potential is generate in the initial segment and not in the soma because the concentration of voltage gated sodium channels is less in the soma than in initial segment.

Electrical Events During Neuronal Inhibition

As shown in figure C when inhibitory neurotransmitter is released it causes influx of chloride ions and or out flux of potassium ions from soma. This causes resting membrane potential to become more negative that is from 65 to 70mV this is called hyperpolarization or inhibitory postsynaptic potential. (IPSP)

Cont:
Presynaptic inhibition: inhibition of presynaptic neuron can also be achieved by another way that is by inhibiting presynaptic nerve fiber or its terminal before it releases its excitatory neurotransmitter. This is called presynaptic inhibition. GABA is involved in this type of inhibition which causes opening of anion channels. Presynaptic inhibition occurs in many of the sensory pathways in CNS.

Properties of Chemical Synapses

1. Dales Law single neurotransmitter. 2. One way transmission presynaptic to postsynaptic. 3. Minimum synaptic delay 0.5m/sec. Causes: Discharge of neurotransmitter. Diffusion. Binding with receptor proteins. Increaser in membrane permeability. Inward diffusion of sodium ions to produce action potential.

Cont:
Importance: By measuring delay time one can estimate the number of neurons involved in a circuit or whether the reflex action is monosynaptic, bisynaptic or polysynaptic. 4. Convergence / divergence. 5. Spatial & temporal summation.

6. Facilitation or subliminal fringe.

7. Occlusion.

8.

Fatigue of synaptic transmission.

When excitatory synapses are repeatedly stimulated at a rapid rate, the number of discharges by postsynaptic neuron is at first very great, but then it gradually decreases or many case. This is called fatigue or synaptic transmission. Mechanism of fatigue: It occurs due to partial exhaustion of stores of neurotransmitter in presynaptic terminals. Importance: By this property the excess excitability of brain during an epileptic fit is finally subsided so that the seizure ceases.

Cont:
9. Effect of alkalosis or acidosis on synaptic transmission Alkalosis - neuronal excitability e.g epileptic fits develop when pH of the ECF is from 7.4 to 7.8 or 8.0 Acidosis - neuronal activity e.g during diabetic or uremic acidosis when pH from 7.4 to 7.0 10. Effect of hypoxia on synaptic transmission Adequate oxygen supply is required for normal excitability. When there is hypoxia this decreases neuronal excitability. For example lack of arterial supply to brain for 3 7 seconds results in unconsciousness.

Cont:
11. Effect of drugs on synaptic transmission CAFFEINE Coffee THEOPHYLLINE - Tea THEOBROMINE Cocoa all increase neuronal excitability by reducing the threshold for excitation of neurons. STRYCHNINE - neuronal excitability by inhibiting action of some of inhibitory neurotransmitters like glycine in the spinal cord sever tonic muscle spasm. Lipid soluble anesthetics inhibit neuronal activity by increasing threshold of excitation.