# Investigating the role of BNST GluN2D subunit-containing NMDARs in ethanol-induced plasticity and behavior

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2021 · $65,610

## Abstract

PROJECT SUMMARY/ABSTRACT
Alcohol use disorder (AUD) is a chronic, relapsing disease, highly comorbid with anxiety and depression. In
fact, these states of negative affect experienced during withdrawal are hypothesized to drive alcohol seeking
and relapse behavior. The bed nucleus of the stria terminalis (BNST) is a key brain region responsible for the
integration of negative affect and alcohol-related behaviors. Within this highly heterogeneous region, synaptic
plasticity driven by ethanol exposure is a significant contributor to maladaptive behavior. N-methyl-D-aspartate
receptors (NMDARs) are a major target of ethanol, known to modulate BNST synaptic plasticity and
transmission following both acute and chronic exposure. However, to date, no work has investigated the role of
GluN2D-subunit containing NMDARs in mediating ethanol’s effects in the BNST. Moreover, these subunits are
expressed by corticotropin-releasing factor (CRF)-positive BNST neurons (BNSTCRF), a key subpopulation for
driving anxiety-like and ethanol seeking behaviors. Together, these data suggest a role for GluN2D expression
in regulating ethanol intake and reward following chronic ethanol exposure. Thus, I propose a series of
experiments to investigate the role of BNST GluN2D-containing NMDARs in ethanol-induced plasticity and
behavior, with a focus on BNSTCRF neurons. First, I will assess the ability of GluN2D expression to regulate
ethanol sensitivity of BNSTCRF neurons. Second, I will dissect the contribution of GluN2D-containing NMDARs
to altered glutamatergic plasticity of BNSTCRF neurons following chronic ethanol exposure. Lastly, I will test the
hypothesis that abstinence following chronic ethanol exposure regulates GluN2D-containg NMDAR expression
in a behaviorally relevant manner.

## Key facts

- **NIH application ID:** 10312440
- **Project number:** 1F32AA029592-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Marie Althea Doyle
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,610
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312440

## Citation

> US National Institutes of Health, RePORTER application 10312440, Investigating the role of BNST GluN2D subunit-containing NMDARs in ethanol-induced plasticity and behavior (1F32AA029592-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10312440. Licensed CC0.

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