Functional Neuroanatomy of

the Limbic System

Alex Dranovsky, M.D., Ph.D.
Assistant Professor of Clinical Psychiatry
Columbia University
 Why Functional and Why a
Psychiatrist?
1. How to conceptualize the limbic system
- a Psychiatrist’s perspective
• Hypothalamus and basic drives
• Amygdala and emotional salience
• Hippocampus and the integration of novelty
• VTA - Accumbens and reward contingency
• Other structures
 Limbic System
• MWD - Limbic system noun Date:1952: a group of subcortical
structures (as the hypothalamus, the hippocampus, and the
amygdala) of the brain that are concerned especially with
emotion and motivation

• WIKIPEDIA ­

The limbic system is a term for a set of brain structures 
including the hippocampus and amygdala and anterior thalamic 
nuclei and a limbic cortex that support a variety of functions 
including emotion, behavior and long term memory. 
What defines the Limbic System?
• Limbic Lobe - “a ring of cortical tissue that
surrounds the brain stem” - Paul Broca 1800’s

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 Definition II
• Klüver and Bucy
– Removal of Temporal lobes in Rhesus Monkeys
results in
• Indiscriminant hypersexuality
• Complete loss of fear
• Dulling of emotional expression
• Increased oral exploration
» Arch of Neurol Psych 1939
• Bilateral temporal lobe damage in humans
• Hypersexuality, inappropriate oral and tactile exploration,
memory deficits, flattened emotions, and bulimia
Definition III
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Arch Neur Psych, 1937

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A Psychiatrist’s Perspective

• A Structural Model
– ID - Instinctual
Needs/Drives
– Superego - Moralizing
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– Ego - An organizing
mediator
 Why Functional and Why a
Psychiatrist?

1. Hypothalamus and basic drives

2. Amygdala and emotional salience
3. Hippocampus and the integration of novelty
4. Nucleus Accumbens and reward contingency
5. Cingulate and higher cortical function
Hypothalamus as the center for drives

• Sex
• Feeding
• Osmoregulation
• Sleeping
• Pair bonding
• Stress response
 Hippocampus
• Deep temporal lobe structure that runs anterio-
posterior parallel to the parahippocampal gyrus.
•
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– Perforant pathway from the entorhinal cortex QuickTimeª and a

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• Cholinergic (EXC) - med septal nuc -> throughout

• GABAergic (INH) - msn -> to GABA interneurons
– Modulatory systems -> throughout
• LC, Raph, VTA
• Posterior hypothalamus - GABA, Histamine
• Major outputs
– Subiculum - throughout neocortex and other
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• Contralateral hippocampus
• Septum
• Hypothalamus (mammillary bodies)
 Intrahippocampal circuitry
• Tri-synaptic circuit with collateral and contralateral
connections
• Highly organized subregions with dense and
redundant connections
• Especially adapted for pattern separation.

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 Hippocampal Plasticity
• Changes in the external world result in
SUSTAINED molecular, cellular, and physiologic
changes in the hippocampus in rodents
– Positional changes -> changes in ensemble
representations
– Chronic Stress -> dendritic shrinkage and decreased
neurogenesis
– Antidepressant treatment -> dendritic complexity and
increased neurogenesis
– Learning -> LTP
 Hippocampal Function I
• Temporal lobectomy disrupts recent
memories (HM)
– Distant memory is in tact
– Procedural memory is in tact
• Depression, PTSD, Schizophrenia
– Decreased hippocampal volume
– Decrease is proportional to time spent in disease
state
• Stress
– Decrease volume
– GR and MR receptors in all subfields
– Direct regulation of the hypothalamus stress
response
 Hippocampal Function II

• Identification of sensory stimuli as

NOVEL is one function of the
hippocampus that ties together its role
in memory, learning, stress response,
and place representation
 Amygdala
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• Complex of nuclei deep to the

piriform cortex in the rostral end of
the temporal lobe

• Structure-function groups of nuclei

– Corticomedial
– Basolateral
– Central

• Contralateral connectivity via the stria

terminalis and the anterior
commissure
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outputs

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 Amygdala Function I
• Fear
– Klüver and Bucy -
Complete loss of fear

– Necessary for fear learning QuickTimeª and a

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• FC potentiates
dorsolateral synaptic
plasticity
 How can you prove that Amygdala
mediates fear learning?
• Classical Conditioning
– UCS -> UCR
– UCS+CS -> UCR
– CS -> CR

• The ability of a neutral CS QuickTimeª and a

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CR serves as a model for
emotional learning
 Amygdala Function II
(It’s not just for fear…)
• Rodent models
– The same holds true for appetitive memories
– ITS NOT THE VALENCE, IT’S THE
SALIENCE

• Urbach-Wiethe disease (Lipoid Proteinosis)

– No enhancement of memory by emotional
content
– ITS NOT THE VALENCE, IT’S THE
SALIENCE

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 Amygdala Function III
The assignment of salience
• fMRI hyperactivity to emotional faces
– in patients with Social Phobia
– in patients with PTSD
– compared to neutral faces in normal controls
• fMRI hypoactivity to emotional faces
– In patients with Autism

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 Modulators of emotional
learning
• Norepinephrine release in the amygdala potentiates
formation of fear memories
– Beta adrenergic receptor blockers diminish FC
– Beta adrenergic receptor blockers diminish fMRI signal
– Clinical implications

• Extinction - repetitive presentation of CS without UCS

results in loss of CR
– D-cycloserine administration in the amygdala potentiates
extinction of fear memories
– Clinical implications
Dopamine comes from the VTA

• Cell bodies of dopaminergic

neurons reside in the VTA of
the midbrain
– Tuberoinfundibular
– Mesocortical
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– Mesolimbic
 Mesolimbic projections
• Outputs
– A major tract to the nucleus accumbens
– Projections to other limbic structures

• Inputs
– Medial forebrain bundle major tract from
the forebrain
– Inputs from Amygdala, Hippocampus,
Hypothalamus, Thalamus and many
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 What’s in this for me?

• upon evaluating sensory QuickTimeª and a

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information and
performing associative
learning the brain must
compute a reward
contingency before
performing a motor
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output
 Drugs of Abuse
• Almost all compounds that have the ability to
stimulate the VTA -> NA pathway are
substances of abuse across species
• Electrical stimulation can induce self-
administration
• MFB stimulation can directly induce relapse
“best feeling ever”

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 VTA -> NA

• Manipulating reward contingency is the

greatest molder of behavior
 Other tidbits
• Brain stem nuclei produce all of the brain’s
serotonin, norepinephrine, and dopamine
• Septum
– Major relay for hippocampal projections to the
anterior thalamic nucleus
– Also meeting point for anterior comissure
– Overlying hypothalamus
– ? Relay station for generalization
• Major cortical projection areas
– Cingulate gyrus
• Anterior region is hyperactive in depression
• Current focus of brain stimulation research
– Medial orbitofrontal area
Putting it all together: physiology
• A Structural Model
– ID - Instinctual Needs/Drives
– Superego - Moralizing Conscience
– Ego - An organizing mediator

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Putting it all together: disease

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• Autism
• Anxiety disorders
• Schizophrenia
• Depression
• Alzheimers disease
• Substance abuse
• Personality disorders