Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalmic-Pituitary-Adrenal...
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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.

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Introduction 3310699

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

Introduction

  • Amygdala, hippocampus, and medial prefrontal cortex influence HPA axis

  • LimbicBNSTPVN

  • BNST subdivided


The big point

The Big Point

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


Nijsen paper background information

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


Methods and materials

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)


Methods and materials1

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


Methods and materials2

Methods and Materials

  • Lesions identified

    • Needle track

    • Loss of neurons

    • Gliosis (increase in size and number of astrocytes)


Animals included

Animals included

  • Bilateral damage included

  • Partial unilateral lesions removed

  • Missed lesions removed


Results

Results

  • Anterior BNST lesions damage fusiform and dorsomedial nuclei

  • Posterior BNST lesions damage principle, interfascicular, and transverse nuclei


C fos crh gad 65 mrna expression in bnst

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


Successful lesions

Successful Lesions


C fos mrna expression

C-Fos mRNA expression


Plasma acth

Plasma ACTH

  • 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

Plasma ACTH graph


Plasma corticosterone

Plasma Corticosterone

  • Increased B to restraint

  • Anterior lesion decreased B at 30 min

  • Posterior lesion increased B at 60 min


Plasma cort graph

Plasma Cort graph


Posterior bnst lesion and the hpa axis

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


Posterior bnst

Posterior BNST

  • 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

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


Discussion

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


Mcgill paper

Crh gene expressed in BNST

Encodes CRH

Increased anxiety and stress

Overexpression HPA dysfunction

McGill Paper

308/Y

WT


Nijsen paper

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


Discussion1

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


The end

The End


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