# Interneurons tune the neural circuits mediating the anxiolytic effects of alcohol

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2020 · $370,240

## Abstract

Project Summary
Excessive alcohol consumption leads to alcohol use disorders in approximately 7% of individuals and is
associated with numerous health conditions, substantial economic burden, and is the third leading cause of
preventable deaths in the United States. Despite the fact that alcohol misuse is a serious health and economic
concern worldwide, we still do not fully understand the basic mechanisms contributing to alcohol consumption.
One primary factor thought to drive consumption is the anxiolytic effects of alcohol. However, the specific cell
types and networks mediating the anxiolytic effects of alcohol are unknown. Recent studies have elucidated
connections between the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) in the network
communication of anxiety. Oscillations within the BLA and mPFC and the coupling between these regions is
thought to be driven by parvalbumin (PV) interneurons in the BLA. PV interneurons in the BLA express the
GABAAR δ subunit at a high density, which is thought to be a target of action for alcohol. We hypothesize that
alcohol acts preferentially on PV interneurons in the BLA, modulating local oscillations and frequency coupling
between the BLA and mPFC, thereby mediating the anxiolytic effects. This proposal represents the first
attempt to examine the cell type-specific effects of alcohol on the network communication of anxiety. The
current application will explore the cell type-specific targets of alcohol in the BLA and determine whether the
GABAAR δ subunit on PV interneurons plays a role in mediating the anxiolytic effects of low dose alcohol
(Specific Aim 1). This application will determine whether the anxiolytic effects of alcohol involve modulation of
the local oscillations in the BLA and mPFC as well as the frequency coupling between the mPFC and BLA
(Specific Aim 2). Further, we will determine whether driving the network communication of safety recapitulates
the anxiolytic effects of alcohol and whether disruption of the pro-safety communication reduces the anxiolytic
effects of alcohol (Specific Aim 3). This proposal will define specific cell types and associated neural pathways
that are most sensitive to alcohol and how these circuits orchestrate sensitivity to alcohol. This application will
determine whether the anxiolytic effects of alcohol are mediated by GABAAR δ subunit containing receptors on
PV interneurons in the BLA through the coordination of activity between the mPFC and BLA.

## Key facts

- **NIH application ID:** 9976409
- **Project number:** 5R01AA026256-03
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Jamie Lynn Maguire
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,240
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976409

## Citation

> US National Institutes of Health, RePORTER application 9976409, Interneurons tune the neural circuits mediating the anxiolytic effects of alcohol (5R01AA026256-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9976409. Licensed CC0.

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