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Alcohol-Induced Alternative Splicing in Drosophila Memory Circuits

Award Number: F31AA030219
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 04/06/2025

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Alcohol-Induced Alternative Splicing in Drosophila Memory Circuits - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$8,981 )
2026	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	000	3	12/16/2025	NON-COMPETING CONTINUATION	-$8,981
														Subtotal = -$8,981

Issue Date FY: 2024 ( Subtotal = $48,974 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	000	3	6/25/2024	NON-COMPETING CONTINUATION	$48,974
														Subtotal = $48,974

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	000	2	6/7/2023	NON-COMPETING CONTINUATION	$47,694
														Subtotal = $47,694

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	003	1	5/25/2022	NEW	$0
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	002	1	5/25/2022	NEW	$716
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	000	1	2/10/2022	NEW	$46,036
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Alcohol Research Programs	001	1	3/2/2022	NEW	$0
														Subtotal = $46,752

Grand Total All Awards = $134,439

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Alcohol-Induced Alternative Splicing in Drosophila Memory Circuits

Award Number: F31AA030219

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 04/06/2025

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