Transcript LimbSysGS08

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 imaging
2. No consistent theoretical context.
Components of
Limbic Systems
1. Periaqueductal gray; PAG
2. Hypothalamus/HPA Axis
3. Amygdala
4. ACC/insula
5. MCC
6. DRN/LC
7. Autonomic Nervous System
Limbic Structures & Key Functions
1. PAG Coordinated behaviors; Autonomic/Skeletal
2. Hypothalamus/HPA Axis Autonomic/hormonal control
3. Amygdala Simple significance codes/valences; mostly fear
4. Anterior cingulate (ACC) & Insula
Store Emotional/Valenced information
Recode amygdala
5. Midcingulate cortex (MCC)
Predict outcomes & Resolve ambiguity
Select outputs; mental or movement decisions
Devise new behaviors for new problems
6a. Dorsal Raphe Nucleus (DRN) Regulate mood
6b. Locus coeruleus (LC) Coordinate responses to events &
Enhance valenced memories
7. 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
Primary & Secondary Emotions
Structures that regulate ANS/Fight-or-Flight
Central Amygdala
Subgenual ACC
PVN, Hypothalamus
Ventrolateral PAG
LC
PAG: Coordinates Emotional Behaviors
Generates Primary Emotions
1. Location
2. Two Functional Modes
3. Norepinephrine (NE)/LC Selects F-or-F Mode
Electrical Stimulation of Hypothalamus
(VMH/Lat) or PAG Evokes Integrated Behaviors
1. Location
2. Stimulated Defense
or Eating
3. Stroke/tumors to Hypothal PAG can produce Sham Rage
Fully integrated rage without external control
e.g., a fly on nose & excess rage
PAG Regulates ANS via Projections to
NTS, DMX, IML
Hypothalamus Controls Hormone Response: HPAA
1. Pituitary Location
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
3. NE/LC Drives PVN
HPA Axis
Amygdala & Fear
1. Location
2. Central nucleus regulates cardiovascular output
Lateral nuclei receive sensory cortex input for
coding significance/valence
Kluver-Bucy Syndrome follows amygdala damage
a. Docility b. Absence of emotional expression
c. Paucity of social interactions
d. Hyperorality/obesity e. Visual agnosia
f. Impaired short-term memory
Amygdala stores simple significance codes mainly for fear
(hissing snake, growl of dog, raised knife, flushed face)
Amygdala Involved in
Fear Perception, ANS Response & Memory
3.
1.
2.
5.
Memory of
object/event
6.
NE/LC Enhances Negative Memories
4.
Case of Bilateral Amygdala Damage
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 nonconscious 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
Affect & Motivation in Cingulate Gyrus (Flat map)
1. Location
ACC
MCC
2. ACC
Stores Valenced
Memories
Regulates ANS
3. MCC: Resolves conflict
Regulates skeletomotor output
ACC Stores Memories of Sad Events
Positron Emission Tomography (PET) study
of healthy women remembering sad events
Summary of
functional
imaging studies of
simple emotions
Fear, 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 fear
at 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 + correlations
Blue – correlations
This connection
disrupted in
depression &
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, pushing
Activities that are valenced & context dependent
CinguloSpinal/Layer Vb Projection Neurons
I
II
IIIab
IIIc
Va
Vb
VI
MCC Directly Regulates Skeletomotor
Behavioral & Emotion Relevant Activity
Facial Region of the Cingulate Motor Area:
Expressing & Interpreting Emotional States
All emotions can impact
the facial region in ACC
The Facial Region Projects
to the Facial Motor Nuc;
Muscles of facial expression
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 of
Complex Emotions Requires ACC
Context resolves complex
and ambiguous emotional
states
Can you now understand
what this woman is saying
with her face?
LC Pivotal to F-or-F Systems
LC regulates HPA axis via PVN &
ANS by projections to NTS/DMX
Locus Coeruleus
Mediates F-or-F & Emotional Memories
LC & PVN are reciprocally connected
Activation of the PVN by allostatatic-stress signals
from prefrontal/cingulate cortices drive LC
LC 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)
1. Located in
Midbrain
2. Serotonergic (5HT) neurons
3. Project to forebrain
(Amygdala & ACC)
4. Determines tonic activity
The DRN
Regulate
Mood
Limbic Diseases Are Associated with
Disordered Behaviors
Depression
Reduced reactivity to the environment &
Lack of emotional responsivity
Anxiety and sometimes panic
Traits are genetic predispositions
associated with
behavioral & neuronal phenotypes
Prodromal Depression:
Predisposition before Symptoms
1. Up to 70% cases inherited
2. Short variant polymorphism in 5HT Transporter;
Chromosome 17q12
Reduces transcription efficacy of the 5HTT
3. Associated with trait anxiety and risk of depression
“Normals” with Short 5HTT allele
Shrunken sACC & Amygdala
1. Reduced Functional
Interaction of
sACC & Amygdala
2. Amygdala uncontrolled by ACC/MCC
associated with enhanced fear – anxiety
Major Depression State with
Reduced ACC Size & Sad Activation
Positron Emission Tomography study of glucose metabolism
Highest 5HTT Density in ACC
Citalopram binds to 5HTT
Heaviest binding in ACC accounts for clinical efficacy of
selective serotonin reuptake inhibitors (SSRI); paroxetine
5HT Therapeutic Targets for Depression
Pharmacotherapy for Depression
Enhance 5HT Function in ACC & Amygdala