The Limbic System and Cerebral Circuits for Emotions, Learning and Memory

Introduction to the Limbic SystemAnatomically 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.

Anatomical Location + discussion of components.Structure and function of the hippocampal formation.The Amygdaloid nucleus complex and the function of its 3 components.Links between the limbic system and effector (behaviour) systems.Links between neurotransmitter-specific projection systems and the limbic system.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

Anatomical Location and Overview.Limbic association cortex surrounding diencephalon-medial + inferior (orbital) surface cingulate gyrus, parahippocampal gyrus, orbital gyrus, temporal pole.

Limbic System: Cortical AreasFigs. 16-2 and 3Note: 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).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)AfferentEfferent

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

Hippocampal CircuitsFornixbranch(PostcommisuralBranch)Fornix(Precommissural)(septal-hippocampal pathway) Affects - Theta rhythm (4-8Hz)(Hippocampal commissure)(Perforant & alvear path)AfferentsEfferentsHIPPOCAMPUS(Cortico-entorhinal projections)ERC/Sub(PHG)CortexSeptal nucleiMammillary BodyContralateralHippocampus1. & 2.3.4.

The Hippocampus Dentate Complex(HC-DG)Afferent PathwaysPyramidal cell(CA1,2) PHG (ERC, Sub)Perforant Pathway: PHG (ERC) --> DG Also .Alvear Pathway: PHG --> CA1 Septo-hippocampal path (via fornix): Septal nuclei --> DGHippocampal 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 bodiesThalamic nucleimammillothalamictractCingulate gyrusEntorhinal cortexHippocampalformationInput for memory consolidation

Korsokoffs 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 (Ammons horn): CA1, CA2, CA3, CA4 (hilus) [CA = coronus ammonis].

Medial Temporal Circuitry See Fig. 16-18 for Corresponding Anatomy SectionAdjacent MTL cortices : Entorhinal (ERC), Perirhinal (PRC) Parahippocampal (PHC)Hippocampus (HC) proper : Dentate Gyrus (DG), CA3, CA1, and Subiculum (Sub)PRCPHCERCSubDGCA 3CA 1FornixPyramidal cellsPyramidal cellsSchaffercollateralsPyramidal cellsGranule cellsMossyfibers

The HippocampusCA fieldsA) Lateral Ventricle, B) ependymal glia (ventricular surface), C) Alvear Layer, (pyramidal axons) 3 layers of hippocampus (archicortex): Polymorph Layer (pyramidal axons & basket cells (-))Hippocampal pyramidal layer (pyramidal cell bodies)Molecular Layer (pyramidal dendrites)A) Lateral ventricleB) Ependymal gliaC) Alvear layer1. Polymorph Layer2. Pyramidal Layer3. 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 SystemsSquire 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 MTLSuffered head injury @age 9Developed severe epilepsy

Surgeon surgically removed the medial temporal lobe bilaterally

HM suffered severe anterograde and temporally graded retrograde amnesia

Spared skill learning

III. AmygdalaAlmond-shapedMajor 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) SystemsNeuroendocrine by amygdala (central and CM) via paraventricular n. of hypothalamus.Autonomic by amygdala (central n.?) lateral hypothalamus descending pathways via autonomic nuclei.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 SystemsThis 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 Alzheimers Disease.

Cholinergic System(Fig. 2-2)

DANE5-HTFig. 2-2

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

*******