Psychological and Physiological Stress: PVN and Amygdala

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Psychological and Physiological Stress PVN and
Amygdala

• Topics in Stress Immunity
• John McGlone, Professor
• Reference Papers
• Kovacs et al., 2005
• Akirav and Richter-Levin, 2005

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Outline

• Afferent and Efferent Pathways in the PVN
• Acute vs. Chronic Stress
• Mapping CRF and c-fos
• Regions in the PVN and Stressor effects on each
  PVN region
• Amgdala Function and Anatomy
• Amygdala role in Stress
• What other brain regions are involved in stress?

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Afferent and Efferent Pathways in the PVN

• Afferent means neurons from outside the PVN that
  enter the PVN some afferent signals are from
  sensory cells and others are from other brain
  regions
• Efferent means neurons that exit the PVN and go
  elsewhere some efferent neurons go to other
  brain regions and others go to the periphery

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Afferent Pathways
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Efferent Pathways
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Physiological Vs. Psychological Stressors

• Physiological stressors
• Homeostatic or systemic
• Physical
• Autonomic and anatomical changes are clear (HR,
  BP, Piloerection, etc.)
• Often a discrete stress (clear on and off)

• Psychological Stressors
• Neurogenic or emotional
• No physical interaction is required, but it may
  be present
• More cortex activation usually more severe
  response
• Often variable application of stress (ex., social
  stress only when defeated)

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Stress Intensity Acute vs. Chronic

• Acute
• Single exposure
• High or low intensity ex., increasing
  temperature

• Chronic
• Either
• repeated (chronic intermediate) or
• continuous
• High or low stress ex., repeated social defeat
  (severe or not)

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Habituation

• Animals habituate to repeated stressor
• Habituation Decrement (usually to baseline) of
  HPA activation with repeated (chronic
  intermediate or continuous) stress
• CRF habituates more commonly than AVP
• Habituation is due to higher brain inhibition (or
  lack of activation) of PVN
• AVP may increase over time when stressed --
  facilitation

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Other Important Factors

• Priming effects
• Genetic differences strains of rodents, families
  of farm animals
• Others?

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Markers of Cell Activation

• What is c-fos?
• C-fos is an intermediate-early gene (IEG) that is
  activated in all cells when they are activated
• Baseline c-fos is low or non-detectable
• It peaks at 30-60 minutes after cell is activated
• Other fos-family antigens are activated in a
  different time frame

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Markers of PVN Activation

• CRF
• Only parts of the PVN are activated
• Peaks 5-30 minutes after acute stress
• Does not show neuronal inhibition very well
• Is in nucleus and axon

• c-fos
• Typically, only CRF and AVP neurons will respond
  in the PVN to stress
• Does not show neuronal inhibition very well
• Only in or near the nucleus

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PVN Nuclei

• DP dorsal parvocellular (NE CRF)
• MP medial dorsal parvocellular (CRF)
• VMP ventromedial parvocellular (NECRF)
• MC magoncellular (AVP
• Parvocellular CRFAVP (hypophysiotropic CRF)
• Magnocellular stress-responsive AVP, ex.
  dehydration

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C-fos activation of the PVN
AVP
All less CRF
Not so much NE CRF and AVP
No AVP mostly CRF
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Questions

• Which PVN nuclei are expected to be activated
  early and later in
• Acute Social stress?
• Chronic Cold stress?
• Dehydration?
• Foot shock?

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The Limbic System
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Olfactory-Limbic System
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Limbic Amygdala -- Caudate
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Limbic -- Hippocampus
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Amygdala Fear, Emotion

• It is 3 collections of nuclei (about 10 in
  total) the 3 main amygdaloid nuceli are
• Basolateral nucelus (BL)
• Centromedial group (Ce-M) composed of the Central
  and Medial nuclei The Ce-M is connected to the
  hypothalamus via the Stria Terminalis
• Cortical nucleus also known as the olfactory
  amygdala
• Morphology similar to the cerebral cortex with
  pyramidal cells

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Nuclei within the AmygdalaLess commonly
discussed, the VNAg
Vomeronasal Amygdala
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Amygdala, Memory Stress
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To be Acutely Stressed, You Must

• Perceive the situation as stressful (through
  afferent inputs to the brain)
• Have no control over the stress impingement
• Arouse the Limbic System (hippocampus, amygdala,
  cortex and/or others)
• Have a certain PVN response
• Have certain efferent responses depending on the
  stressor, genetics, timing, etc.

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To Experience Chronic Stress, You Must

• Experience all that is in acute stress, and
• Not have adapted or habituated
• Remember
• Believe in the neocortex that the experience is
  stressful that is, not inhibit the stress
  response through cortical afferents to the PVN

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Questions

• Which other brain regions do you think would have
  c-fos activity 30 minutes after the onset of
  stress? If you dont know the brain region,
  say the region controlling heart rate, for
  example.
• What would be the advantage of double staining
  for CRF and c-fos in the same cells of the PVN?

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Questions

• Can an animal that has spinal cord damage and
  lost afferent inputs to the brain feel pain in
  a limb? Explain
• Can an animal that has lost efferent connections
  from the brain to a limb feel pain? Explain
• Does a person in a coma or under general
  anesthesia experience stress, say cold stress?

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Design an Experiment

• Pick a stress
• Pick acute or chronic
• What will you measure in the brain?
• At what time(s) will you sample after stress?
• What endocrine measures will you collect and in
  what fluids or tissues?
• What species?
• How many animals per treatment? Why? How did you
  determine this?