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Introduction

Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs. Dennis C. Choi, Amy R. Furay, Nathan K. Evanson, Michelle M. Ostrander, Yvonne M. Ulrich-Lai, and James P. Herman. Introduction.

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Introduction

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  1. Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs Dennis C. Choi, Amy R. Furay, Nathan K. Evanson, Michelle M. Ostrander, Yvonne M. Ulrich-Lai, and James P. Herman

  2. Introduction • Amygdala, hippocampus, and medial prefrontal cortex influence HPA axis • LimbicBNSTPVN • BNST subdivided

  3. The Big Point • Subregions of the BNST differentially regulate HPA axis responses to acute stress

  4. Nijsen Paper: background information • BNST is involved in autonomic and behavioral reactions • BNST is a rostral forebrain structure • Enclosed by lateral ventricle, lateral septum, fornix, nucleus accumbens, preoptic area, and hypothalamus • Links amygdala and hippocampus with PVN and brain stem

  5. Methods and Materials • 36 male Sprague Dawley rats (275-300g) • 3/cage • Food/water ad libitum • Temp and humidity controlled • 12h light/dark (Lights on at 6am)

  6. Methods and Materials • Day 1: Surgery • Days 2-8: Recovery • Day 8: Restraint stress (9:30-10:30am) • Day 9-15: Nonhandled recovery • Day 16: 2nd restraint stress and killed • Killed 30 min after restraint for peak of c-fos

  7. Methods and Materials • Lesions identified • Needle track • Loss of neurons • Gliosis (increase in size and number of astrocytes)

  8. Animals included • Bilateral damage included • Partial unilateral lesions removed • Missed lesions removed

  9. Results • Anterior BNST lesions damage fusiform and dorsomedial nuclei • Posterior BNST lesions damage principle, interfascicular, and transverse nuclei

  10. C-fos, CRH, GAD 65 mRNA expression in BNST • C-fos decreased with anterior lesion • CRF decreased with anterior lesion • GAD 65 decreased with anterior lesion • GAD 65 diminished with posterior lesion • \ lesions were successful

  11. Successful Lesions

  12. C-Fos mRNA expression

  13. Plasma ACTH • Elevated at 30 and 60 min (all groups) • Posterior lesion elevated • Anterior lesion no effect • Same at 0 or 120 min (all)

  14. Plasma ACTH graph

  15. Plasma Corticosterone • Increased B to restraint • Anterior lesion decreased B at 30 min • Posterior lesion increased B at 60 min

  16. Plasma Cort graph

  17. Posterior BNST lesion and the HPA axis • Increased secretion of ACTH and B • Increased c-fos mRNA • Increased CRH and AVP mRNA in PVN • Inhibits HPA response to stress

  18. Posterior BNST • Restraint induced c-fos expression enhanced by lesion • Principal nucleus inhibits the PVNmp • Principal nucleus regulates HPA activity

  19. Anterior BNST lesion and the HPA axis • Decrease B and c-fos • No alteration of CRH and AVP in PVN • CRH and Glu activate HPA

  20. Discussion • Specific roles of BNST nuclei • Anterior excites PVN, promotes B secretion • Posterior inhibits PVN excitation, ACTH release, and B responses • Posterior lesion enhances c-fos expression

  21. Crh gene expressed in BNST Encodes CRH Increased anxiety and stress Overexpression HPA dysfunction McGill Paper 308/Y WT

  22. Nijsen Paper • Restraint stress induces c-fos expression • Stress activates the CRH system in BNST • Not directly related to autonomic stress • Site of CRH determines response • CRH in medial BNST stress induced

  23. Discussion • BNST is a “clearing house” to regulate HPA • Posterior BNST inhibits HPA activity to restraint • Lesioning primary nuclei increased • ACTH and B • C-fos mRNA • CRH and AVP

  24. The End

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