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Dissecting the Cellular and Molecular Mechanisms Underpinning Single Neuron Computation

Award Number: R01NS153223
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Dissecting the Cellular and Molecular Mechanisms Underpinning Single Neuron Computation - Project Summary PI:Clandinin and Druckmann The transformation of synaptic inputs into axonal outputs represents a fundamental building block of brain computation. Decades of work has described remarkable variation in these input-output transformations across cell types, yet our mechanistic understanding of how single neurons implement specific computations in vivo remains limited. The overarching goal of this project is to develop biologically constrained biophysical models of single-neuron computations, thereby fulfilling a longstanding ambition of neuroscience In this context, the proposed work focusses on two fundamental questions. What input-output transformations do single neurons implement in vivo? What are the cellular and molecular mechanisms that constrain these computations? We hypothesize that well constrained models will reveal new principles underpinning the ability of single neurons to robustly compute behaviorally critical signals. To test this hypothesis, we leverage the fruit fly, which affords unique access to powerful stimulus manipulations, has a wealth of genetic tools for cell-specific measurements and perturbations of neural activity, and has a highly stereotyped connectome, all of which provide essential constraints to biophysical models. In this system, we will use cutting edge sensors of neuronal activity, acousto-optical deflector microscopy, genetic perturbations, super-resolution microscopy and machine learning to build biologically realistic biophysical models of computations that share deep homology with computations in retina and cortex. This work will reveal generalizable principles of neuronal computation that will inform our understanding of neural circuit function across species. Finally, by identifying critical cellular and molecular parameters that constrain single neuron computation, these studies will inform our understanding of healthy brain function, potentially informing therapeutic strategies that would restore these parameters in disease.


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 = $531,625 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/19/2026	NEW	$531,625
														Subtotal = $531,625

Grand Total All Awards = $531,625

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Dissecting the Cellular and Molecular Mechanisms Underpinning Single Neuron Computation

Award Number: R01NS153223

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/21/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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