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“CRCNS: Computational principles of memory based decision making in Drosophila”

Award Number: R01DC020123
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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“CRCNS: Computational principles of memory based decision making in Drosophila” - Decision making largely depends on the integration of prior sensory experiences that are stored in the brain as memories. One of the best-understood model systems of a two-choice decision process is associative olfactory memory in Drosophila. In the fly, learning occurs at the synapse between Kenyon cells (KCs) and mushroom body output neurons (MBONs). By pairing olfactory stimuli with a reward or a punishment flies can reliably learn to distinguish two initially neutral odors. As in mammals, dopaminergic neurons (DANs) represents this contextual valence and modulate the strength or connectivity of KC>MBON synapses within distinct compartments of the MB, consequently altering behavior. To understand how this decision making is encoded in memory we thus must first understand the computation performed within individual DAN-KC-MBON modules. In preliminary work, we built a realistic computational model of the MBON-3 neuron including the precise synaptic connectivity all 948 innervating KCs based on the complete synaptic connectome of the MB. Our model incorporates precise membrane properties of the MBON-3 neuron that we obtained by performing patch-clamp recording in vivo. We demonstrate that MBON-3 is electrotonically compact and show that activation of complex KC input patterns reflecting physiological activation by individual odors in vivo are sufficient to robustly drive MBON spiking. Here, we will combine experimental analysis in vivo with computational modelling to determine the mechanisms controlling MBON activation under baseline conditions and in response to memory-induced plasticity. We will identify the minimal number of KCs and KC synapses required for robustMBON activation for different subsets of approach and avoidance MBONs in vivo. These data will guide computational approaches to identify general and specific features of the KC-MBON interactions. The results will then serve to identify compartment-specific plasticity mechanisms in vivo, and corresponding computational mechanisms in silico. Finally, we extend these approaches to simultaneous analyses at multiple KC-MBON modules to provide a computational basis for decision-making.


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 = $0 )
2026	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	3	12/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $197,696 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	3	7/18/2023	NON-COMPETING CONTINUATION	$197,696
														Subtotal = $197,696

Issue Date FY: 2022 ( Subtotal = $197,696 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	001	2	6/24/2022	NON-COMPETING CONTINUATION	$197,696
2022	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	1	10/18/2021	NEW	$0
														Subtotal = $197,696

Issue Date FY: 2021 ( Subtotal = $204,246 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Research Related to Deafness and Communication Disorders	000	1	7/26/2021	NEW	$204,246
														Subtotal = $204,246

Grand Total All Awards = $599,638

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“CRCNS: Computational principles of memory based decision making in Drosophila”

Award Number: R01DC020123

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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