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
• Amygdala, hippocampus, and medial
prefrontal cortex influence HPA axis
• LimbicBNSTPVN
• BNST subdivided
The Big Point
• Subregions of the BNST differentially
regulate HPA axis responses to acute
stress
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
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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
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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
• Lesions identified
– Needle track
– Loss of neurons
– Gliosis (increase in size and number of
astrocytes)
Animals included
• Bilateral damage included
• Partial unilateral lesions removed
• Missed lesions removed
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 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
C-Fos mRNA expression
Plasma ACTH
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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 Corticosterone
• Increased B to restraint
• Anterior lesion decreased B at 30 min
• Posterior lesion increased B at 60 min
Plasma Cort graph
Posterior BNST lesion and the HPA
axis
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Increased secretion of ACTH and B
Increased c-fos mRNA
Increased CRH and AVP mRNA in PVN
Inhibits HPA response to stress
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
• Decrease B and c-fos
• No alteration of CRH and AVP in PVN
• CRH and Glu activate HPA
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
308/Y
WT
• Crh gene expressed
in BNST
• Encodes CRH
• Increased anxiety and
stress
• Overexpression
HPA dysfunction
Nijsen Paper
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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
• 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