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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 Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Amygdala, hippocampus, and medial prefrontal cortex influence HPA axis
- LimbicBNSTPVN
- BNST subdivided

The Big Point Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Subregions of the BNST differentially regulate HPA axis responses to acute stress

Nijsen Paper: background information Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- 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

Methods and Materials Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

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

Methods and Materials Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- 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

Methods and Materials Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Lesions identified
- Needle track
- Loss of neurons
- Gliosis (increase in size and number of astrocytes)

Animals included Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Bilateral damage included
- Partial unilateral lesions removed
- Missed lesions removed

Results Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Anterior BNST lesions damage fusiform and dorsomedial nuclei
- Posterior BNST lesions damage principle, interfascicular, and transverse nuclei

C-fos, CRH, GAD 65 Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic InputsmRNA 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

Successful Lesions Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

C-Fos mRNA expression Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

Plasma ACTH Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Elevated at 30 and 60 min (all groups)
- Posterior lesion elevated
- Anterior lesion no effect
- Same at 0 or 120 min (all)

Plasma ACTH graph Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

Plasma Corticosterone Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Increased B to restraint
- Anterior lesion decreased B at 30 min
- Posterior lesion increased B at 60 min

Plasma Cort graph Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

Posterior BNST lesion and the HPA axis Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Increased secretion of ACTH and B
- Increased c-fos mRNA
- Increased CRH and AVP mRNA in PVN
- Inhibits HPA response to stress

Posterior BNST Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Restraint induced c-fos expression enhanced by lesion
- Principal nucleus inhibits the PVNmp
- Principal nucleus regulates HPA activity

Anterior BNST lesion and the HPA axis Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- Decrease B and c-fos
- No alteration of CRH and AVP in PVN
- CRH and Glu activate HPA

Discussion Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- 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

Crh gene expressed in BNST Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

Encodes CRH

Increased anxiety and stress

Overexpression HPA dysfunction

McGill Paper308/Y

WT

Nijsen Paper Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- 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

Discussion Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

- 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

The End Differentially Regulate Hypothalmic-Pituitary-Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

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