# Striatal Microcircuit Dynamics of Ethanol Habits

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $540,790

## Abstract

Project Summary
 The research proposal explores how a habit center in the brain, the dorsolateral striatum, is disinhibited
by chronic alcohol exposure to foster habit formation. Understanding how this process works at molecular,
neural circuit and behavioral levels is critical to devising novel therapeutic strategies targeting alcoholism, as
well as comorbid habitual use of other substances of abuse. Dorsolateral striatum output is powerfully
governed by the inhibitory fast-spiking interneuron (FSI) population. FSIs are in relatively high abundance in
the dorsolateral striatum as compared to other striatal subregions, which positions these cells to be key
modulators of dorslolateral striatum output and habit expression. As a minority population of neurons in the
striatum, FSIs and their role in chronic ethanol exposure-induced habit formation is vastly understudied. This
proposal seeks to understand how chronic ethanol exposure dampens FSI function to allow for dorsolateral
striatum disinhibition and habitual action expression. This will be investigated in three specific experimental
aims employing cutting-edge technology that allows for an unprecedented view into the function of these
neurons in mice. In the first aim we test the hypothesis that chronic ethanol exposure depresses the release of
the inhibitory neurotransmitter GABA from FSIs onto postsynaptic medium spiny neurons, which are the output
neurons of the striatum. This will be accomplished using optogenetics coupled with brain slice
electrophysiology. In the second aim we explore FSI synchrony. FSIs synchronize their activity to enhance
their inhibitory authority over dorsolateral striatum output. Thus, we will test the hypothesis that FSIs
desynchronize following chronic ethanol exposure. We will test this using slice electrophysiology and calcium
imaging of FSI activity in awake behaving mice exposed to chronic alcohol. Finally, we will test the contribution
of dampened FSI release of GABA and FSI asynchrony on alcohol drinking and generalized habit learning in
mice. By examining how ethanol hijacks the neural circuitry of habit formation, the results of this study should
significantly advance our knowledge toward novel therapeutic strategies targeting alcoholism and provide
novel insight to myriad neuropsychiatric disorders involving striatal dysfunction.

## Key facts

- **NIH application ID:** 9900690
- **Project number:** 5R01AA024845-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** BRIAN NEIL MATHUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,790
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900690

## Citation

> US National Institutes of Health, RePORTER application 9900690, Striatal Microcircuit Dynamics of Ethanol Habits (5R01AA024845-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9900690. Licensed CC0.

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