# Chromatin remodeling in GABA neurons contributes to alcohol use disorder

> **NIH NIH K01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $156,205

## Abstract

Alcohol misuse affects millions of people, resulting in numerous deaths each year. People who are
resistant alcohol intoxication and sedation are more likely to consume high levels of alcohol (binge
drinking) and are at higher risk of developing alcohol use disorder. One mechanism underlying the
development of alcohol use disorder is neuronal plasticity, which involves the regulation of gene
expression. How chromatin-mediated gene regulation in GABAergic neurons contributes to alcohol-
induced sedation and tolerance is unknown. My preliminary data using Assay for Transposase-
Accessible Chromatin by sequencing (ATAC-seq) shows that the chromatin landscape in GABA
neurons is altered by alcohol exposure, particularly in genes associated with insulin receptor signaling.
I propose to investigate relevant neuronal pathways identified by ATAC-seq to evaluate how chromatin
remodeling affects alcohol sedation and tolerance. Further, my preliminary data indicate that alcohol
alters gene regulation in GABA neurons, especially in genes that play a role in the insulin receptor
pathway. Finally, I propose to identify GABA neuron subtypes and to develop genetic tools that allow
subtype-specific manipulation, which will then be used to investigate how GABA neuron subtypes are
involved in alcohol use disorders. These activities will identify potential therapeutic targets for alcohol
use disorders. While I have experience in single-neuron physiology, I require additional training to
become a successful independent investigator. Thus, my immediate career goals are to obtain
extramural funding and produce manuscripts to establish expertise in alcohol-related research. My
long-term career goals are to become an independent investigator and establish a successful research
program investigating the role of GABAergic neurons in alcohol use disorder. This proposal leverages
my previous training in single-neuron physiology and will provide extensive additional training in
Drosophila model systems, the mechanisms of alcohol abuse, and bioinformatic analysis. I anticipate
that each aim will produce at least two scientific manuscripts and will provide preliminary data for future
R01 applications. Therefore, completing the activities proposed here will enable my transition to an
independent principal investigator.

## Key facts

- **NIH application ID:** 10371484
- **Project number:** 1K01AA029200-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Collin Merrill
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $156,205
- **Award type:** 1
- **Project period:** 2022-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371484

## Citation

> US National Institutes of Health, RePORTER application 10371484, Chromatin remodeling in GABA neurons contributes to alcohol use disorder (1K01AA029200-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10371484. Licensed CC0.

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