# Investigating tonic and synaptic excitatory signaling in the bed nucleus of the stria terminalis across models of alcohol exposure

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $40,100

## Abstract

Abstract/Project Summary
While the effects of alcohol use disorder (AUD) on glutamatergic signaling have been widely reported, the role
of delta glutamate receptors (GluD1 and GluD2) in AUD remains unknown. Although they are not involved in
traditional excitatory synaptic responses to glutamate, the GluD family is known to mediate many subtler aspects
of excitatory signaling which may contribute to the dysfunctions of neuronal activity observed in models of AUD.
GluD1 has also been implicated in AUD by several genome-wide association studies. However, no research has
been conducted directly evaluating the effect of alcohol exposure on GluD1 function.
The bed nucleus of the stria terminalis (BNST) is a forebrain nucleus that has been heavily implicated as a critical
hub for neuromodulation following alcohol exposure. Previous work has shown that alcohol exposure regulates
synaptic glutamate in the BNST, but the exact mechanisms by which this happen remain unclear. Synaptic
glutamatergic transmission is in part mediated by AMPA receptors, ~30% of which can pass calcium (calcium-
permeable AMPARs, CP-AMPARs). Our preliminary data suggests that acute withdrawal from chronic
intermittent ethanol vapor exposure (CIE) decreases both CP-AMPAR synaptic current and reduces a GluD1
mediated tonic excitatory current in the BNST. Although it has been observed before that GluD1 is expressed in
the BNST, these are the first data to that they may be involved in regulating BNST signaling. These data also
implicate GluD1 modulation as a possible novel target for neuromodulation following alcohol exposure. This
proposal aims to further examine the role of CP-AMPARs and GluD1 in the BNST, how they may interact, and
how they are affected by alcohol exposure using a combination of fluorescent in situ hybridization, patch-clamp
electrophysiology, and ex vivo calcium imaging. Aim 1 will use GluD1 knockout (GluD1 KO) mice and wildtype
(WT) littermates to establish a functional profile of GluD1 in the BNST, as well as its overlap with CP-AMPAR
expressing BNST cells. Aim 2 will then evaluate the impact of CIE on BNST CP-AMPAR and GluD1 expression
and signaling, neuronal excitability, and spontaneous calcium dynamics in these mouse models. Finally, Aim 3
will use these approaches to examine the translational relevance of BNST CP-AMPAR and GluD1 signaling
across different models of AUD.

## Key facts

- **NIH application ID:** 10931384
- **Project number:** 5F31AA031177-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sara Yi-Ling Conley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,100
- **Award type:** 5
- **Project period:** 2023-09-14 → 2025-11-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10931384

## Citation

> US National Institutes of Health, RePORTER application 10931384, Investigating tonic and synaptic excitatory signaling in the bed nucleus of the stria terminalis across models of alcohol exposure (5F31AA031177-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10931384. Licensed CC0.

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