The Limbic System and Cerebral Circuits for Emotions, Learning

and Memory

Introduction to the Limbic System

• Anatomically refers to areas surrounding the diencephalon (limbus = border) and bordering the cerebral cortex.

• The “C”-shaped hippocampal formation and includes the amygdala, cingulate and parahippocampal cortices.

The key to learning, memory, and behavior (including emotional behavior) – of paramount importance in psychiatry.

I. Anatomical Location + discussion of components.

II. Structure and function of the hippocampal formation.

III. The Amygdaloid nucleus complex and the function of its 3 components.

IV.Links between the limbic system and effector (behaviour) systems.

V. Links between neurotransmitter-specific projection systems and the limbic system.

VI.Regional Anatomy of these structures.

The Limbic System

The Medial Temporal Lobeand Hippocampus

Anterior section: Amygdala(Fig. 16-13)

Divisions or nuclei of amygdala

Posterior section: Hippocampus, Fornix(Fig. 16-15)

Divisions or nuclei of hippocampal formation

Midsagital section(Fig. 16-19)

Note the mammillary body, mammillothalamic tract, and fornix (body).

Parasagital section(Fig. 16-19)

Note the hippocampal formation, fornix, and amygdala

I. Anatomical Location and Overview.

A. Limbic association cortex – surrounding diencephalon

-medial + inferior (orbital) surface cingulate gyrus, parahippocampal gyrus, orbital gyrus, temporal pole.

Limbic System: Cortical AreasFigs. 16-2 and 3

Note: surroundingdiencephalon, medial +inferior (orbital) surface [cinglulate gyrus, parahippgyrus, orbital gyrus, temporal pole].

These cortices are near otherassociation cortices and projectto:

B. the Hippocampal Formation and Amygdala (Fig. 16-1).Note the “C” shape, along with the major output paths for the hippocampus: the fornix.

Note the mammillary body: it is part of what structure?Refer to Table 16-1 – Lists all the components of the limbic system.

Look!!

II. Hippocampal Formation:ComponentsA subcortical structure composedof allocortex.A central function:Consolidation of STMs intoLTMs (+ many other limbicfunctions through complexinterconnections).

Note the 3 components

Neocortex and Allocortex(Fig. 16-12)

More on these 3layers later

Hippocampal Formation:Circuitry (Fig. 16-4).A.Components and structure – a banana-shaped structure with its components (dentate, hipp,subiculum) folded upon one another like a “jelly roll”.Inputs are from entorhinalcortex, which collects infofrom other association areasdentate gyrus hipp formation + subculumoutput to fornix andalso back to entorhinal cortex(See Fig. 16-6).

Hippocampal Formation:Input and Output (Fig. 16-6)

Afferent

Efferent

Serial and Parallel Processing of Hippocampal Circuits (Fig. 16-5)

Hippocampal Circuits

Fornix

bran

ch

(Postcomm

isuralB

ranch)

Fornix

(Pre

com

mis

sura

l)(septal-hippocampal pathway) Affects - Theta rhythm (4-8Hz)

(Hippocampal commissure)

(Perforant & alvear path)

AfferentsEfferents

HIPPOCAMPUS(Cortico-entorhinal projections)

ERC/Sub(PHG)

Cortex

Septal nuclei

Mammillary Body

ContralateralHippocampus

1. & 2.

3. 4.

The Hippocampus Dentate Complex(HC-DG)

Afferent Pathways

Pyramidal cell(CA1,2)

PHG (ERC, Sub)

1. Perforant Pathway: PHG (ERC) --> DG Also ….2. Alvear Pathway: PHG --> CA1 3. Septo-hippocampal path (via fornix): Septal nuclei --> DG4. Hippocampal commissure (connects bilateral hippocampi)

Dentate gyrus (granule cells)

(mossy fibers)

Pyramidal cell(CA3)

(schaffer collaterals)

1. (perforant path)

(Also note: this efferent path closes the HC circuit loop!)

2. (alvear path)

Septal nuclei3. (septo-hippocampal path - thru fornix)

Papez’ Circuit:

Fornix mammillary bodies

Thalamic nuclei

mammillothalamictract

Cingulate gyrus

Entorhinal cortex

Hippocampalformation

Input for memory consolidation

• Korsokoff’s Syndrome: thiamine deficiency (i.e., from alcoholism) degeneration of mammillary bodies.

• Other output: via entorhinal cortex to a number of association areas, involve the prefrontal cortex (control of mood and behaviours).

C. Anatomy and Information Flow in Greater Detail.

Cytoarchitechture dimensions of hippocampus (Ammon’s horn): CA1, CA2, CA3, CA4 (hilus) [CA = coronus ammonis].

Medial Temporal Circuitry –See Fig. 16-18 for Corresponding Anatomy Section

Adjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC)

Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub)

PRC

PHC

ERC

Sub

DG CA 3

CA 1

Fornix

Pyramidal cells

Pyramidal cells

Schaffercollaterals

Pyramidal cells

Granule cells

Mossyfibers

The HippocampusCA fields

A) Lateral Ventricle, B) ependymal glia (ventricular surface), C) Alvear Layer, (pyramidal axons)

3 layers of hippocampus (archicortex): 1. Polymorph Layer (pyramidal axons & basket cells (-))2. Hippocampal pyramidal layer (pyramidal cell bodies)

3. Molecular Layer (pyramidal dendrites)

A) Lateral ventricleB) Ependymal glia

C) Alvear layer

1. Polymorph Layer

2. Pyramidal Layer

3. Molecular Layer(pyramidal dendrite)

(pyramidal axon)

(pyramidal cell body)

Imaging the Human Hippocampus is Challenging

Hippocampal Formation(Fig. 16-18)

Anatomy of Hippocampal Formation(Fig. 16-18)

Taxonomy of Long-term Memory Systems

Squire L, Zola S PNAS 1996;93:13515-13522Adapted from Squire, Knowlton 1994

(Corkin, Amaral, Gonzalez, Johnson and Hyman J. Neuro, 1997)(Scoville and Milner, 1957)

Patient H.M. and the Human MTL

• Suffered head injury @age 9– Developed severe epilepsy

• Surgeon surgically removed the medial temporal lobe bilaterally

• HM suffered severe anterograde and temporally graded retrograde amnesia

• Spared skill learning

III. Amygdala

• Almond-shaped

• Major function: Responding to stimuli with an emotional component.

• 3 Nuclear components:

A. Basolateral – attaching emotional significance to a stimulus.

Sensory cortices (higher-order) BL limbic associaation cortex, prefrontal cortex, hippocampal formation (for learning emotional significance).

B. Central Nucleus – mediates emotional responses.

Visuaosensory input from solitary, parabrachial nuclei CN dorsal motor n. of X, other parasympathetic n. reticular formation and hypothalamus autonomic responses.

C. Corticomedial nuclei – mediates behaviors triggered by olfactory stimuli.

Olfactory bulb CM hypothalamus (lateral zone) regulation of “appetitive behaviours”; i.e., eating in response to smells.

Amygdala(Fig. 16-7A)

Amygdala(Fig. 16-7B)

Amygdala(Fig. 16-7C)

IV. Links Between Limbic System and Effector (Behavioural) Systems

A. Neuroendocrine – by amygdala (central and CM) via paraventricular n. of hypothalamus.

B. Autonomic – by amygdala (central n.?) lateral hypothalamus descending pathways via autonomic nuclei.

C. Somatic Motor – by several limbic components reticular formation stereotypic behaviour via reticulospinal tract.

Fig. 16-9: Links between Limbic System and Effector Systems

V. Links Between Neurotransmitter-Specific Projection Systems and Limbic Systems

This projection appears to be vital for normal thoughts, moods, and behaviours.

We have known this empirically because of known behavioural disturbances in animals with lesions of these systems and neurotransmitter-activating or –blocking drugs seem to help humans manage behavioural aberrations to some degree.

Dopamine: Excessive transmission in limbic structures may contribute to schizophrenia.

5-HT: Ascending projections control mood; increase appears to help in many forms of anxiety and depression (mood disorders).

Norepinephrine: Excessive transmission may contribute to anxiety and aggression. Under-reaction, along with that of 5-HT, may contribute to depression.

Acetylcholine: Important in cognition, activating a number of neocortical, as well as limbic areas – the 1st system to degenerate in Alzheimer’s Disease.

Cholinergic System(Fig. 2-2)

DA NE

5-HT

Fig. 2-2

VI. Regional Anatomy

See outline and stained sections of structures (Figs. 16-13, 15, 19).