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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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slide1

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