Limbic & Autonomic Systems

Brent A. Vogt, Ph.D.

Limbic Systems by Iversen, Kupfermann, Kandel

Page 984“Feelings are cognitive translations of

ambiguous peripheral signals.”

What is a feeling?

Limbic Systems by Iversen, Kupfermann, Kandel

Page 987“The limbic system consists of the limbic

lobe and deep lying structures.”

In light of Fig. 50-4, is the hippocampus part of the limbic system?

Limbic Systems by Iversen, Kupfermann, Kandel

Page 994“The hippocampus has only an

indirect role in emotion.”

Is the hippocampus part of the limbic system and is it involved in emotion?

Limbic Systems by Iversen, Kupfermann, Kandel

Page 988“The amygdala is the part of the limbic system most specifically involved with

emotional experience.”

What does “most specifically” mean? Are there less specific involvements?

What is emotional experience?

Limbic Systems by Iversen, Kupfermann, Kandel

What is the limbic system?What are its functions?

What is emotional information?

Fig 50-8 only shows emotion as output from Central nuc of Amygdala

Is that the only limbic/emotion nucleus?

Limbic Systems by Iversen, Kupfermann, Kandel

The major problems in limbic system research are

1. Failure to integrate human imaging2. No consistent theoretical context.

Components of Limbic Systems

1. Periaqueductal gray; PAG 2. Hypothalamus/HPA Axis3. Amygdala 4. ACC/insula5. MCC6. DRN/LC

7. Autonomic Nervous System

Limbic Structures & Key Functions

1. PAG Coordinated behaviors; Autonomic/Skeletal2. Hypothalamus/HPA Axis Autonomic/hormonal control3. Amygdala Simple significance codes/valences; mostly fear4. Anterior cingulate (ACC) & Insula

Store Emotional/Valenced information Recode amygdala

5. Midcingulate cortex (MCC)Predict outcomes & Resolve ambiguitySelect outputs; mental or movement decisionsDevise new behaviors for new problems

6a. Dorsal Raphe Nucleus (DRN) Regulate mood 6b. Locus coeruleus (LC) Coordinate responses to events &

Enhance valenced memories7. Autonomic Nerv Sys (ANS) Supports skeletomotor output &

Enhances CNS memory of valenced objects/events

Emotion Involves Valencing Objects/Events

Emotional Motor Systems

for Expressing Emotion

Structures that regulate ANS/Fight-or-FlightCentral AmygdalaSubgenual ACC

PVN, HypothalamusVentrolateral PAG

LC

Primary & Secondary Emotions

PAG: Coordinates Emotional BehaviorsGenerates Primary Emotions

3. Norepinephrine (NE)/LC Selects F-or-F Mode

1. Location

2. Two Functional Modes

3. Stroke/tumors to Hypothal PAG can produce Sham RageFully integrated rage without external control

e.g., a fly on nose & excess rage

1. Location

2. Stimulated Defense or Eating

Electrical Stimulation of Hypothalamus (VMH/Lat) or PAG Evokes Integrated Behaviors

PAG Regulates ANS via Projections to NTS, DMX, IML

2. Limbic cortex drives PVN to secrete CRH into portal veins. CRH evokes release of ACTH from the pituitary which evokes release of cortisol from adrenal cortex. Cortisol binds glucocorticoid rec. to ↑ glucose levels & metabolism, amino acid metabolism, fat breakdown, release of neutrophils & ↑ memory

Hypothalamus Controls Hormone Response: HPAA

1. Pituitary Location

3. NE/LC Drives PVNHPA Axis

2. Central nucleus regulates cardiovascular outputLateral nuclei receive sensory cortex input for

coding significance/valence

Kluver-Bucy Syndrome follows amygdala damagea. Docility b. Absence of emotional expression

c. Paucity of social interactionsd. Hyperorality/obesity e. Visual agnosia

f. Impaired short-term memory

1. Location

Amygdala & Fear

Amygdala stores simple significance codes mainly for fear(hissing snake, growl of dog, raised knife, flushed face)

Amygdala Involved inFear Perception, ANS Response & Memory

Memory of object/event

NE/LC Enhances Negative Memories

1. 2.

3.

4. 5.

6.

Lipoid proteinosis with rage & loss of recent memory& complete loss of the amygdala (white arrows)

SM-046 could not judge intensity of facial fear. She understood non-threatening faces and made

judgments with verbal information. She could draw fearful faces from memory & prompting but claimed

they were not accurate.

Amygdala codes for objects and events of non-conscious or conscious fear.

Behavior after amygdala damage reflect miscoding of fearful events, lead to excessive risk taking, odd

relations & financial decisions.Symptoms of amygdala damage

Case of Bilateral Amygdala Damage

Affect & Motivation in Cingulate Gyrus (Flat map)

2. ACCStores Valenced

MemoriesRegulates ANS

3. MCC: Resolves conflictRegulates skeletomotor output

1. Location

ACCMCC

ACC Stores Memories of Sad Events

Positron Emission Tomography (PET) study of healthy women remembering sad events

Summary of functional

imaging studies of simple emotionsFear, Sadness & Happiness are

segregated

ACC Mediates ANS Activity With the Amygdala

ACC projects to autonomic brainstem: Nuc of Solitary Tract & DMX

Stimulation at V evoked pure fearat H evoked “desire to leave room”

Amygdala Projects to ACC

Axon terminal labeling (dots)Monkey[3H] Amino acid injection(hatched)

Amygdala & Cingulate Cortex Interact During Fear

Red/yellow + correlationsBlue – correlations

This connection disrupted indepression &posttraumatic stress disorder

Electrical Stimulation of MCC Evokes Complex Skeletomotor Responses adapted to Context

lip puckering,finger kneading,

bilateral limb movements(not single muscle/muscle groups like motor cortex)

Kissing, scratching, pushingActivities that are valenced & context dependent

I

II

IIIab

IIIc

Va

Vb

VI

I

II

IIIab

IIIc

Va

Vb

VI

CinguloSpinal/Layer Vb Projection Neurons

MCC Directly Regulates Skeletomotor

Behavioral & Emotion Relevant Activity

Facial Region of the Cingulate Motor Area:Expressing & Interpreting Emotional States

The Facial Region Projects to the Facial Motor Nuc;

Muscles of facial expression

All emotions can impactthe facial region in ACC

Interpreting Internal Emotional States:Empathy

Facial ambiguity is not resolved in

amygdala

What is this bride’s face saying about her emotional state ?

ACC uses context information

Internal State and Expression ofComplex Emotions Requires ACC

Context resolves complex and ambiguous emotional

states

Can you now understand what this woman is saying

with her face?

LC regulates HPA axis via PVN &ANS by projections to NTS/DMX

LC Pivotal to F-or-F Systems

Locus CoeruleusMediates F-or-F & Emotional Memories

LC & PVN are reciprocally connectedActivation of the PVN by allostatatic-stress signals

from prefrontal/cingulate cortices drive LCLC releases NE in thalamus, amygdala, and cortex to

enhance memories associated with ANS output; i.e., beating heart and heavy breathing

Storage of memories of valence codes in amygdala and significance/context in ACC

depends on NE/LC

LC/NE Integrates Limbic Motor Systems

1. NTS/PVT mediate heart rate responses in sACC/Central Amyg

2. PAG:NE selects F-F

3. PVN drives HPA Axis;NE, ACTH, Cortisol

4. Enhances Amygdala processing & memory

Overview of Limbic Motor Systems

Dorsal Raphe Nuclei (DRN)

2. Serotonergic (5HT) neurons3. Project to forebrain(Amygdala & ACC)

4. Determines tonic activity

1. Located in Midbrain

The DRN Regulate Mood

Limbic Diseases Are Associated withDisordered Behaviors

Depression Reduced reactivity to the environment &

Lack of emotional responsivityAnxiety and sometimes panic

Traits are genetic predispositionsassociated with

behavioral & neuronal phenotypes

Prodromal Depression:Predisposition before Symptoms

1. Up to 70% cases inherited2. Short variant polymorphism in 5HT Transporter;

Chromosome 17q12Reduces transcription efficacy of the 5HTT

3. Associated with trait anxiety and risk of depression

2. Amygdala uncontrolled by ACC/MCC associated with enhanced fear – anxiety

“Normals” with Short 5HTT alleleShrunken sACC & Amygdala

1. Reduced Functional Interaction of

sACC & Amygdala

Major Depression State withReduced ACC Size & Sad Activation

Positron Emission Tomography study of glucose metabolism

Highest 5HTT Density in ACC

Citalopram binds to 5HTTHeaviest binding in ACC accounts for clinical efficacy ofselective serotonin reuptake inhibitors (SSRI); paroxetine

5HT Therapeutic Targets for Depression

Pharmacotherapy for DepressionEnhance 5HT Function in ACC & Amygdala