# Presynaptic structure and function in ethanol tolerance development

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, MERCED · 2022 · $177,364

## Abstract

Project Summary / Abstract
A single acute ethanol exposure causes lasting changes in behavior and brain function. Acute changes may
form a foundation for progressive changes with subsequent ethanol exposures, incrementally increasing the
risk of alcohol use disorder. We found evidence of structural changes in presynaptic active zones in neurons
that promote behavioral plasticity (tolerance, preference, and reward), in response to acute ethanol in
Drosophila. In mammals there is much evidence for electrophysiological and circuit driven changes in
presynaptic activity in models of AUD. However, molecular changes at presynapses remain difficult to
measure, making assessment of the mechanistic coding of plasticity incomplete. Advances in Drosophila
transgenics and microscopy resolution let us determine the effects of ethanol on evolutionarily conserved
presynaptic architecture. We hypothesize that presynaptic changes contribute to the coding of ethanol-induced
behavioral plasticity, to bias the behavioral and circuit effects of subsequent ethanol exposures. The goal of
this exploratory grant proposal is to gain a mechanistic handle on ethanol-induced presynaptic change in
Drosophila. The long-term goal is to develop a new approach towards understanding how alcohol changes the
structure and function of the brain, that can be applied across a variety of model organisms for addiction
research, and combined with rigorous physiological and circuit-level understanding. To accomplish our goal,
we will perform three independent experiments. First, We will ask how widespread presynaptic plasticity is
found in the seats of Drosophila learning and memory. Second, we will ask about the role of presynaptic
plasticity genes in ethanol-induced presynaptic change. Third, we will ask if presynaptic change is due to a
property of the circuitry upstream and downstream of the sites of change. We predict that the study outcome
will define specific presynaptic sites that show ethanol-induced plasticity. This information will allow us to
explore the functional role of synapse assembly and maintenance pathways, and homeostatic versus Hebbian
mechanisms, taking into account the neurotransmitter and neuromodulator synaptic profiles.

## Key facts

- **NIH application ID:** 10492451
- **Project number:** 5R21AA029178-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, MERCED
- **Principal Investigator:** FREDERICK W WOLF
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $177,364
- **Award type:** 5
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492451

## Citation

> US National Institutes of Health, RePORTER application 10492451, Presynaptic structure and function in ethanol tolerance development (5R21AA029178-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10492451. Licensed CC0.

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