# Cerebellar Contributions to Alcohol Use Disorders

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $344,250

## Abstract

Project Summary/Abstract
Alcohol (ethanol; EtOH) abuse is a leading cause of death and disability, making our understanding of the
mechanisms that affect transition from healthy use of EtOH to development of an alcohol use disorder (AUD) a
high biomedical priority. In this context, the initial neurological responses to socially relevant concentrations of
EtOH (5-20mM), and individual differences in those responses are thought to play a critical role in determining
vulnerability or resilience to development of AUD. Thus, it is crucial to identify molecular targets and neural circuit
responses to low concentrations of EtOH, and to identify the mechanisms by which such responses vary across
individuals with high or low risk for developing AUD. In our published and preliminary studies, we have
determined that low concentrations of EtOH (10mM, as would occur in the blood of an average adult human after
consuming 1-2 standard alcoholic beverages) powerfully affect cerebellar granule cell GABAAR currents, but
with opposite polarity in multiple strains of rodents with high and low EtOH consuming phenotypes respectively.
Further, we have discovered a previously unknown direct synaptic connection between the cerebellum and the
ventral tegmental area (VTA), a brain structure known to influence many aspects of EtOH reward and associated
behaviors. These are important discoveries because genetic differences in cerebellar structure, connectivity and
sensitivity to EtOH are known to be associated with risk for developing an AUD in humans and with excessive
EtOH consumption in rodents, but the underlying mechanisms are unknown. The purpose of this proposal is to
advance our understanding of how low concentrations of EtOH affect cerebellar spatiotemporal processing and
behaviors, how such actions vary in strains of mice with divergent EtOH related behavioral phenotypes, and to
characterize the neural circuitry that translates differential actions at a cellular level into differential behavior,
including EtOH reward and excessive EtOH consumption. Success in this endeavor will increase our
understanding of how the cerebellum influences predilection to developing an AUD, and will identify novel
molecular targets for manipulating responses to low concentrations of EtOH. Collectively, such information
should help guide the development of psychological and pharmacological approaches to screening for and
deterring development and maintenance of AUD. We will use a combination of patch-clamp recording from
cerebellar brain slices, patterned optical light stimulation (to simulate in vivo-like network processing), and
behavioral techniques combined with optogenetic manipulations of cerebellar processing to determine how low
concentrations of EtOH affect cerebellar processing and output, and EtOH related behaviors. We will then use
optogenetic tract tracing techniques to fully characterize cerebellar to VTA circuitry and function, which will
provide important insight into t...

## Key facts

- **NIH application ID:** 9985681
- **Project number:** 5R01AA026078-04
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** DAVID J ROSSI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985681

## Citation

> US National Institutes of Health, RePORTER application 9985681, Cerebellar Contributions to Alcohol Use Disorders (5R01AA026078-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985681. Licensed CC0.

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