# Alcohol-Induced Alternative Splicing in Drosophila Memory Circuits

> **NIH NIH F31** · BROWN UNIVERSITY · 2022 · $46,752

## Abstract

Repeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication.
These memories can problematically trigger relapse in individuals recovering from alcohol use disorder (AUD).
The molecular mechanisms by which ethanol changes memories to become long-lasting and inflexible remain
unclear. We recently demonstrated that formation of these memories results in expression of alternative
transcript isoforms in memory-encoding neurons in Drosophila melanogaster. Drosophila rely on mushroom body
(MB) neurons to make associative memories, including memories of ethanol-associated sensory cues.
Decreasing expression of genes that play a role in splicing in adult MB neurons reduces formation of these
memories, demonstrating the necessity of RNA processing in ethanol memory formation. Moreover, decreasing
expression of genes that are alternatively spliced like the Dopamine-2-like Receptor (Dop2R) in adult MB
neurons reduces ethanol memory formation. This suggests that the splicing changes in these genes has
functional implications for future memory formation. The central hypothesis of this proposal is that the dynamic
alternative splicing of Dop2R in response to alcohol exposure directs reward behavior by changing the activity
of neural circuits.
We generated mutant Drosophila that have forced expression of the naïve or trained Dop2R isoform, which
allows us to interrogate how these splice variants affect neural dynamics and behavior at a highly mechanistic
level. The applicant will reveal intracellular localization of DOP2R protein (Aim 1, how alternative splicing of
Dop2R affects reward memory (Aim 2), and plasticity within memory circuits (Aim 3). By completing these aims,
the applicant will gain scientific and technical expertise in cellular neurobiology and neurogenetics, behavioral
assessment of Drosophila, super-resolution imaging, and 2-photon calcium imaging. Through a comprehensive
training plan, this fellowship will facilitate the professional development of the applicant in robust experimental
design and data analysis; written and oral scientific communication; and effective and inclusive mentoring.
Successful completion of the project and training goals are fully supported by the interactive and supportive
institutional environment of Brown University and in the Neuroscience Graduate Program, and will prepare the
applicant for the next steps towards an independent scientific career.

## Key facts

- **NIH application ID:** 10465607
- **Project number:** 1F31AA030219-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Tariq Brown
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465607

## Citation

> US National Institutes of Health, RePORTER application 10465607, Alcohol-Induced Alternative Splicing in Drosophila Memory Circuits (1F31AA030219-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10465607. Licensed CC0.

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