Psychological and Physiological Stress: PVN and Amygdala

1. 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

2. 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?

3. 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

4. Afferent Pathways

5. Efferent Pathways

6. 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) Physiological Vs. Psychological Stressors

7. 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) Stress Intensity & Acute vs. Chronic

8. 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

9. Other Important Factors • Priming effects • Genetic differences; strains of rodents, families of farm animals • Others?

10. 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

11. 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 Markers of PVN Activation

12. PVN Nuclei • DP = dorsal parvocellular (NE + CRF) • MP = medial dorsal parvocellular (CRF) • VMP = ventromedial parvocellular (NE+CRF) • MC = magoncellular (AVP • Parvocellular = CRF+AVP (hypophysiotropic CRF) • Magnocellular = stress-responsive AVP, ex. dehydration

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

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

15. The Limbic System

16. Olfactory-Limbic System

17. Limbic – Amygdala -- Caudate

18. Limbic -- Hippocampus

19. 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

20. Nuclei within the AmygdalaLess commonly discussed, the VNAg Vomeronasal Amygdala

21. Amygdala, Memory & Stress

22. 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.

23. 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

24. Questions • Which other brain regions do you think would have c-fos activity 30 minutes after the onset of stress? [If you don’t 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?

25. 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?

26. 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?