The Limbic System I. Overview a. Between the neocortex and hypothalamus regulates behaviors, integrates with somatic motor output (mediates between needs of Hypothalamus and plans of Neocortex – deals with realities of the moment) b. All structures are implicated in the experience and expression of emotions c. The simplest cortex is around the ventricle, then more complex, then neocortex (see II. Organization) d. Limbic forebrain originated as means of controlling internal environment based on external chemosensory and internal hypothalamic input II. Organization a. Limbic Lobe – Cortical structures i. Allocortex (3 layers) 1. Hippocampus 2. Primary olfactory (prepyriform) cortex ii. Periallocortex (4-5 layers) 1. Entorhinal cortex 2. Perirhinal cortex 3. Proximal cingulate, orbitofrontal, and posterior parahippocampal cortex iii. Proisocortex (“almost” neocortex – 6 layers, but very weak layer4) 1. Cingulate cortex 2. Orbitofrontal cortex 3. Posterior parahippocampal cortex b. Limbic Lobe - Subcortical structures (not organized as cortex – no lamina) i. Basal forebrain ii. Amygdala c. Diencephalon i. Hypothalamus ii. Thalamus (AN, MD) iii. Epithalamus (habenula) d. Mesencephalon – Limbic Midbrain Areas (LMA): i. Ventral tegmental area ii. Central gray and tegmentum III. Sensory input a. Olfaction i. First exteroceptive input = olfactory nerve; at first was thought that cortex developed from an “olfactory cortex” ii. Olfactory information has unique assess to memory systems iii. Unique input to limbic system: 1. Olfactory bulb (2nd order neuron, 1st= olfactory receptor cells) 2. Primary olfactory cortex/amygdala/entorhinal cortex 3. Entorhinal cortex hippocampus *2nd order neuron has direct access to allocortex *no thalamic relay to get to primary cortex (fast) b. Other senses – more indirect, first extensively processed through multiple cortical areas: i. Visual: V1V2V3V4 infratemporal cortices ii. Auditory: A1A2A3A4 etc iii. Primary somatosensory cortex: S1S2S3 S4 etc All go to prefrontal multimodal association cortex (uncommitted) after relay in thalamus IV. Structures and their pathways Structure Function Afferents Efferents Additional info Amygdala -Interpreter of stimuli basic Olf bulb, prim olf cx Olfactory cx Kluver-Bucy syndrome: biological needs and species- Entorhinal cx and hippo Entorhinal, hippocamp damage to amygdala preserving behavior Hypothalamus, MD Hypothalamus, MD agnosia – lack of -Sensory-sensory and sensory- Cingulate, medial Cingulate, medial knowledge of meaning of visceral associations frontal, orbitofrontal cx frontal, orbitofrontal cx stimuli (ie threats, edible Vis, aud, SS assoc cort Vis, aud, SS assoc cort items, peers) Parabrach n-taste, GVA Dorsal prefront. cx Hippocampus -Processes abstract, multimodal via Entorhinal cortex: MMB, AN, septal nuclei Papez circuit: inputs; “biographical memory” prim olf cx, multimodal via fornix Hippo (via fornix) MB for seemingly arbitrary events assoc cortices Cingulate gyrus, AN cingulate gyrus -Learning new facts Amygdala (viscero-sens multimod assoc cortices EC back to hippocampus and sens-sens input) Feedback to entorhinal Cingulate cortex cortex, amygdala *LTP – see below Cingulate Cortex Anterior CC (BA 24)– registers Hypothalamus via MD Entorhinal cortex Cingulum bundle (links averse emotions – suffering, pain Hippocampus – direct Amygdala entire loop) can transect Post. CC (BA 23) – self-perception, and via MMB, AN, MD Multimodal association to eliminate suffering assessment of relevance Amygdala – dir, via MD cortices - parietal and aspect of pain Paleospinothalamic temporal lobes CC involved in conditions tract – via CM (thal) Prefrontal multimodal with disturbed feelings: Multimodal, specific association cortices schizophrenia, autism, sens assoc cortices bipolar disorder, OCDs Prefrontal cortex Averse and rewarding emotions Cingulate cortex Premotor cortex More dorsal areas: attention, Amygdala (dir / via MD) (organize action) executive functions (sequencing, Hippocampus (directly Amygdala, hippocampus planning, abstraction, and via hypothalamus) (report evaluations for organization) Hypothalamus (via MD) memory encoding) Basal forebrain Formation of new memories by Prefrontal assoc cortices Septal n hippocampu *Possibly conveys limbic (septal nuclei, using Ach Amygdala (via VAF) Diagonal band n system interpretations to diagonal band, Hippocampus (viafornix) amygdala, entorhinal, entire telencephalon nucleus basalis) Hypothalamus (via MFB) parahippo, cingulate Limbic midbrain area Nucleus basalis all *Alzheimers: degen of (via MFB) cereb cx, esp prefrontal cholinergic neurons 1) Limbic Midbrain 1)Conveys state of brainstem and Basal forebrain, lateral MMB via mm peduncle area hypothal autonomic, endocrine, hypothal via MFB Brainstem somatic 2)Habenula vegetative and visc mechanisms MMB via mammilo- motor centers 2)Principal relay for basal tegmental tract Autonomic centers (via forebrain input to LMA *fasciculus retroflexus = central tegmental tract) tract fr habenula to LMA DA to Hypothal, Nu accumbens, prefrontal and limbic cortices: from VTA via MFB *The trisynaptic pathway and long-term potentiation - Pathway within the hippocampus: dentate gyrus CA3CA1subiculum - hBetween CA3 CA1: Schaffer collateral system: o Tetanic stimulus (lots of Glu) stimulation of AMPA receptors depolarization enough to drive Mg block out of NMDA channel Ca flows in second messengers o Long-term potentiation (LTP) – neurophysiological model of learning and memory: . Influx of Ca more AMPA receptors (sitting in a pool, “waiting”) to insert into membrane . Increased response to stimulus (more receptors) – reinforces initial arbitrary event = “learned” response . Enhancement lasts hours/days/weeks – reflects “memory” of this event . Also, elongation of dentritic spines after LTP - Further proof of LTP: knock out subunit of NMDA receptor in mouse can’t “learn” maze - LTP also works in cortex, thalamus, striatum, etc. .