Wednesday, October 29, 2025 10/29/2025

BNST circuitry to hypothalamic regions in stress-induced avoidance

Award Number: F31MH132322
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/16/2023
PERIOD OF PERFORMANCE END DATE: 08/15/2026

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BNST circuitry to hypothalamic regions in stress-induced avoidance - PROJECT SUMMARY: Stress can induce long-lasting behavioral changes that result in psychiatric illnesses, such as post-traumatic stress disorder (PTSD). Some of these changes include avoidance of future situations that may be stress- inducing or ignoring one’s own basic needs, such as eating. In mice, stress can manifest in similar ways: after a stress-inducing experience, mice will not explore for food or eat in a novel, brightly lit environment in spite of hunger. This phenomenon of avoidant behavior is known as novelty-suppressed feeding or hyponeophagia. The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that regulates behavioral responses to stress. BNST neural activity is also enhanced in response to uncontrollable stress in humans. Using a mouse model of stressor controllability, our preliminary data establishes that both GABA and glutamate neuron activity within the BNST is increased during uncontrollable stress, extending the previously aforementioned finding in humans to specific BNST neurons. We have also found that BNST neurons form synapses onto key hypothalamic brain regions that play a role in feeding and stress regulation: the arcuate nucleus (ARC) and the paraventricular nucleus of the hypothalamus (PVH). Using RNAscope in situ hybridization, we discovered that the majority of glutamatergic BNST neurons co-express the genetic machinery to vesicularly package both GABA and glutamate. The goal of this proposed project is to determine the synaptic functionality of GABA and glutamate co-transmission from BNST neurons to ARC and PVH in the context of stress-induced avoidance. The principal hypothesis is that there is an increase in co-transmission of GABA and glutamate after uncontrollable stress on downstream ARC and PVH neurons. Therefore, we hypothesize that the GABA-glutamate BNST to hypothalamus pathways are necessary for uncontrollable stress to cause avoidant behavior. A combination of optogenetics, whole-cell electrophysiology, behavioral analyses of stress, and intersectional viral strategies will be used to target and investigate the BNST circuitry to ARC and PVH. In Aim 1, we will evaluate stress-induced changes in GABA and glutamate release from BNST neurons to ARC and PVH. In Aim 2, we will manipulate GABA and glutamate transmission from BNST to ARC and PVH during uncontrollable stress and identify changes in novelty-suppressed feeding. The data generated from this proposed project may identify novel mechanisms of neurotransmitter co-transmission that may be used to reduce the effects of stress on avoidance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $41,986 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	3	8/2/2025	NON-COMPETING CONTINUATION	$41,986
														Subtotal = $41,986

Issue Date FY: 2024 ( Subtotal = $41,422 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	2	7/29/2024	NON-COMPETING CONTINUATION	$41,422
														Subtotal = $41,422

Issue Date FY: 2023 ( Subtotal = $40,142 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	000	1	3/9/2023	NEW	$40,142
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Mental Health Research Grants	001	1	3/9/2023	NEW	$0
														Subtotal = $40,142

Grand Total All Awards = $123,550

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BNST circuitry to hypothalamic regions in stress-induced avoidance

Award Number: F31MH132322

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/16/2023

PERIOD OF PERFORMANCE END DATE: 08/15/2026

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