N375: limbic system

What triggers physical signs of emotion?

Emotionally meaningful stimuli → sensory pathways → hypothalamus → autonomic changes.

Why is the limbic system clinically important?

Virtually all psychiatric disorders involve dysfunction in one or more limbic structures.

Where is the amygdala located?

Anterior temporal lobe, near the hippocampus.

What does the amygdala store & process?

Emotionally significant events. Detects threat & triggers appropriate emotional responses.

Where does the hippocampus sit?

Inside the parahippocampal gyrus, in the inferior horn of the lateral ventricle.

What is the pes hippocampus?

Anterior portion of hippocampus; looks like a kitty paw 🐱.

What is the fimbria?

Initial bundle of hippocampal axons on its surface.

How is the fornix formed?

Two fimbriae curve upward → meet at midline → form body of fornix.

Where does the body of the fornix lie?

Directly on the roof of the thalamus.

Where does the fornix project?

Forward, then down into hypothalamus → splits into two columns → mammillary bodies.

What is the stria terminalis?

Long fiber bundle along the lateral ventricle.

What is the function of the stria terminalis?

Amygdala → hypothalamus connection (emotion → autonomic response).

How does the stria terminalis complement the fornix?

Fornix = hippocampus → hypothalamus;
Stria terminalis = amygdala → hypothalamus.

What does the cingulate gyrus do?

Integrates emotion → behavior (choosing emotional responses).

What does limbic association cortex do?

Gives meaning to emotions; participates in social behavior & self-awareness.

What is the function of the corpus callosum?

Commissural fibers connecting left ↔ right hemispheres.

Where does the cingulate gyrus lie?

Directly on top of the corpus callosum.

What is the alveus?

Thin white matter layer covering the hippocampus.

What is the dentate gyrus?

Granule cell layer; part of the hippocampal formation.

What is the major input pathway into the hippocampus?

Perforant pathway.

What is the sequence of the perforant pathway?

Entorhinal cortex → dentate gyrus (via preforant path)

→ CA3 → CA1 (via schaffer collaterals)

→ fimbria → fornix.

What fibers connect CA3 → CA1?

Schaffer collaterals.

What information does the perforant pathway carry?

Inputs from neocortex, limbic association cortex, amygdala.

Why are the lateral ventricles enlarged in Alzheimer’s disease?

Loss of hippocampal tissue + neuronal atrophy → more CSF space.

Which ventricular portions enlarge most in AD?

Anterior + inferior horns (adjacent to hippocampus).

Where is the limbic association cortex located?

Medial surfaces of frontal, parietal, temporal lobes (mesolimbic cortex).

What is the main function of limbic association cortex?

Interprets memory/emotion; integrates sensory input with emotional meaning.

Examples of structures in limbic association cortex?

Temporal pole, entorhinal cortex, parahippocampal gyrus, cingulate gyrus, subcallosal gyrus, paraterminal gyrus, orbitofrontal cortex.

What was Papez’s key idea?

Emotion generated by a circuit, not a single nucleus. Important in Memory consolidation + emotional experience integration.

What are the three major transition paths in Papez circuit?

• Hippocampus → fornix → mammillary bodies

• Mammillary bodies → MT tract → anterior thalamus

• Anterior thalamus → cingulate → cingulum → hippocampus

What were MacLean’s major updates?

Added amygdala ↔ hypothalamus connections → emotion = fear/reward drives, not just memory.

Added hypothalamus → prefrontal cortex → top-down emotional regulation.

How do amygdala and hippocampus interact?

Amygdala provides emotion (“feelings”), hippocampus provides context (“facts”) → emotional memory formation.

What is the hippocampus’s role in emotion?

Indirect — important for explicit memory, learning from emotional events, contextual recall.

What behaviors occur with amygdala damage?

Tameness, fearlessness, flattened affect → part of Klüver–Bucy syndrome.

What does left hippocampal damage impair?

Auditory/verbal memory (difficulty remembering spoken words).

What does bilateral hippocampal damage cause?

Anterograde amnesia (cannot form new long-term memories). (HM!)

How are the two amygdalae interconnected?

Through the anterior commissure.

what is the lateral amygdala linked to?

Linked to neocortex, especially sensory association cortices.

What does stimulation of lateral amygdala cause?

Fear/anxiety.

What is the medial amygdala connected to?

Striatum + brainstem motor regions. Links emotional meaning → motor output.

Role of the lateral hypothalamus?

Pleasure center — stimulation causes euphoria; animals will self-stimulate intensely.

Role of the ventromedial hypothalamus?

Aversion center — stimulation triggers discomfort, defensive behavior.

What structures form major reward centers?

Septal nuclei + nucleus accumbens.

What effect do dependent drugs have on the Septal nuclei + nucleus accumbens?

Cause dopamine release to these structures

Where do septal nuclei project?

Hypothalamus, amygdala, hippocampus, cingulum, reticular formation.

Bilateral Lesion of Frontal Gyri

Poor concentration, indecisiveness, apathy, loss of initiative.

Bilateral Lesion of Septal Nuclei

Unstable emotions, disinhibition, inappropriate social behavior (Phineas Gage-like).

What does bilateral temporal pole lesion cause?

Fearlessness (loss of fear response).

What does stimulation of the temporal pole cause?

Anxiety, panic, fear.

Bilateral Lesion of Parahippocampal Gyrus

Anterograde amnesia (cannot form new memories).

Where does limbic association cortex receive information from?

Higher-order sensory areas, especially:

• Prefrontal cortex

• Parieto-temporal-occipital association cortex

What does the hippocampus do with limbic association input?

Understands spatial relationships + context; supports memory formation.

Which pathway identifies “what” the object is?

Ventral stream → ventral temporal lobe → amygdala → PTO association cortex.

Which pathway identifies “where” the object is?

Dorsal stream → parieto-temporal-occipital association cortex → hippocampus → PFC.

Where do dorsal + ventral stream emotional signals converge?

Prefrontal association cortex via the cingulum.

After convergence in PFC, where does information go?

Parahippocampal gyrus + amygdala + hippocampus.

Prefrontal/orbital association cortex → hippocampus pathway?

PFC/OFC → cingulate gyrus → hippocampus.

How do other association cortices reach the hippocampus?

Via cingulum → cingulate → hippocampus.

Direct cingulum → hippocampus route?

Cingulum → parahippocampal region → hippocampus.

Temporal/parietal association cortex → hippocampus route?

Lateral temporal/parietal cortex → PHC gyrus → entorhinal cortex → hippocampus.

Amygdala → hippocampus pathway?

Via entorhinal cortex or direct projections.

What are the principle afferents to the hippocampus?

1. PFC/OFC + other association areas

2. Direct cingulum

3. Lateral (temporal/parietal cortex)

4. Temporal association cortex

5. Amygdala (direct)

What is the main exit pathway from the hippocampus?

Fimbria → fornix.

Pathway from mammillary bodies onward?

Mammillary bodies → MT tract → Anterior thalamic nucleus → Cingulate gyrus.

How does the cingulate send info back to hippocampus?

Cingulate → cingulum → PHC gyrus → entorhinal cortex → hippocampus.

Does the hippocampus project directly back to entorhinal cortex?

Yes — forms a feedback loop.

Hippocampus → reward system pathway?

Hippocampus → fornix → septal nuclei (dopamine-mediated pleasure).

Hippocampus → hypothalamus pathway?

Hippocampus → fornix → hypothalamus.

What are the principle eferents from the hippocampus?

1. out the fornix

2. mammillothalamic tract

3. Direct amygdala

4. septal nuclei

5. hypothalamus

Which cortical areas send emotional meaning to the amygdala?

Higher-order temporal & insular cortices.

Olfactory → amygdala route?

Olfactory bulb → piriform cortex → orbitofrontal cortex → amygdala.

What are the principle afferents to the amygdala?

1. Higher-order temporal & insular cortices.

2. Association cortices

3. Olfactory bulbs

4. Thalamus (direct)

5. Brainstem autonomic nuclei (direct)

6. Hippocampus (direct)

Ventral Amygdalofugal Pathway 3 major targets?

1. Medial dorsal thalamus (MD)

2. Hypothalamus

3. Brainstem/reticular formation (DMNV, NTS, autonomic nuclei)

Main functions of ventral amygdalofugal pathway?

• Autonomic/fear conditioning (HR, BP, fight-or-flight)

• Conscious emotional perception + decision making (cingulate, OFC, septal nuclei)

Which cortical areas does the amygdala project to for emotional awareness?

Cingulate gyrus, orbitofrontal cortex, septal nuclei.

Main projections of stria terminalis?

• Hypothalamus (especially VM nucleus)

• Nucleus accumbens (reward)

Functions of stria terminalis outputs?

• Feeding/suckling behaviors

• Autonomic responses

• Reinforcement/addiction pathways (dopamine)

Hyperactivation of amygdala is associated with what disorders?

Anxiety, depression, PTSD, substance abuse.

Classic syndrome involving bilateral amygdala damage? Symptoms?

Klüver–Bucy syndrome.

• Tameness/fearlessness

• Flattened affect

• Hyperphagia

• Hypersexuality

• Visual agnosia

Bilateral hippocampal removal causes what?

Severe anterograde amnesia (no new episodic memories).

Why does Alzheimer’s affect memory early?

Degeneration of hippocampi + mammillary bodies + cortex.

Structures damaged in Korsakoff’s syndrome?

Hippocampi, mammillary bodies, medial dorsal thalamic nucleus.

What two brain regions show dysfunction in schizophrenia?

Hippocampal formation + prefrontal association cortex.

Dopamine hypothesis of schizophrenia?

↑ Dopamine in nucleus accumbens → PFC dysfunction → disorganized thought & behavior.

Why do antipsychotic drugs block dopamine receptors?

To reduce excess dopamine activity → but can cause flat affect/depression.

Where does limbic dopamine originate?

Midbrain → Substantia Nigra (SNc) + Ventral Tegmental Area (VTA).

What tract carries dopamine/serotonin/NE to limbic areas?

Medial forebrain bundle (MFB).

Functions of dopamine in limbic system?

Reward, motivation, learning, addiction.

Where does limbic serotonin originate?

Raphe nuclei (brainstem reticular formation).

What functions does serotonin regulate?

Mood, anxiety, emotional stability, sleep/wake cycles.

How do SSRIs work?

Block serotonin reuptake → ↑ serotonin in synaptic cleft → treat depression/anxiety/OCD.

Where does limbic norepinephrine originate?

Locus coeruleus (in the pons).

Functions of norepinephrine?

Arousal, stress response, attention, emotional learning.

What disorders result from NE neuron degeneration?

Alzheimer’s disease, depression, anxiety, Parkinson’s disease.

Where does limbic ACh originate?

Basal forebrain cholinergic neurons (including septal nuclei).

Functions of acetylcholine in limbic system?

Memory encoding, attention, learning.

Why are cholinesterase inhibitors used in Alzheimer's?

To increase ACh availability as Basal forebrain cholinergic neurons die