# BNST circuitry to hypothalamic regions in stress-induced avoidance

> **NIH NIH F31** · UNIVERSITY OF COLORADO · 2023 · $40,142

## Abstract

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.

## Key facts

- **NIH application ID:** 10680197
- **Project number:** 1F31MH132322-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Annie Ly
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $40,142
- **Award type:** 1
- **Project period:** 2023-08-16 → 2026-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10680197

## Citation

> US National Institutes of Health, RePORTER application 10680197, BNST circuitry to hypothalamic regions in stress-induced avoidance (1F31MH132322-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10680197. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*