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Differential Regulation of HPA Axis Activity by BNST Subregions: Implications for Limbic Integration

This study explores how specific subregions of the Bed Nucleus of the Stria Terminalis (BNST) differentially regulate the hypothalamic-pituitary-adrenal (HPA) axis activity in response to acute stress. Utilizing male Sprague Dawley rats, we performed targeted lesions in the anterior and posterior BNST to assess their effects on HPA axis responses, including plasma ACTH and corticosterone levels. Results indicate that the anterior BNST excites the paraventricular nucleus (PVN) promoting HPA responses, while the posterior BNST inhibits these responses, elucidating their distinct roles in stress regulation.

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Differential Regulation of HPA Axis Activity by BNST Subregions: Implications for Limbic Integration

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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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