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Sustainable Development of MCell4/CellBlender for Realistic Simulation of Synaptic Transmission at Retinal Rod Photoreceptors

Award Number: R50EY038796
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Sustainable Development of MCell4/CellBlender for Realistic Simulation of Synaptic Transmission at Retinal Rod Photoreceptors - Project Summary/Abstract The major goals of this project are to create computational models of retina rod/bipolar/horizontal cell synapses which integrate the empirical findings from the bench experiments of collaborator Prof. Wally Thoreson at University of Nebraska Medical Center, and to further develop MCell/CellBlender in support of these goals. Prof. Thoreson’s research program focuses on understanding glutamate dynamics at rod synapses in the retina, critical for dim light vision, by integrating experimental techniques with advanced computational modeling. Despite the importance of these synapses, key questions about glutamate release and reuptake remain unanswered. Specifically, how postsynaptic rod bipolar cells differentiate random synaptic noise from genuine single-photon signals (the single photon detection problem ) is a significant challenge. Recent data suggests a higher, sustained glutamate release rate than previously thought, highlighting the need for detailed simulations. The program has three aims: Aim 1 will precisely determine glutamate release rates and patterns from rods using advanced optical measurements and electrophysiological recordings in genetically engineered mouse models. Aim 2 will meticulously examine the contributions of glutamate transporters (EAAT1, EAAT2, EAAT5) to regulating synaptic glutamate levels, especially the hypothesized role of EAAT5 as a rapid buffer. Aim 3 will integrate these empirical findings into anatomically detailed Monte Carlo simulations using MCell/CellBlender to explore how release patterns and transporter roles influence glutamate levels and synaptic noise management. The present application provides funding for the Principle Investigator in the role of Research Software Engineer (RSE) who will lead the computational software development and analytical components, bridging experimental neuroscience and computational modeling. This role involves developing and refining MCell models to simulate complex data, modeling transporter kinetics and localization, and leading the integration of empirical findings into comprehensive simulations to test hypotheses related to single-photon detection. The RSE will also tailor software development, validate models, analyze simulation data, and provide specialized training to foster computational neuroscience expertise, as well as dissemination of the open source software and publication of research articles in peer-reviewed publications. This integrated approach is essential for deciphering the intricate mechanisms of glutamate signaling at rod synapses.


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 = $187,500 )
2026	2026	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Vision Research	000	1	7/31/2026	NEW	$187,500
														Subtotal = $187,500

Grand Total All Awards = $187,500

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Sustainable Development of MCell4/CellBlender for Realistic Simulation of Synaptic Transmission at Retinal Rod Photoreceptors

Award Number: R50EY038796

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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