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Molecular determinants of synaptic specificity underlying a visuomotor transformation

Award Number: R00EY036123
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Molecular determinants of synaptic specificity underlying a visuomotor transformation - PROJECT SUMMARY (See instructions): Visuomotor transformations require precise synaptic connectivity between sensory and motor circuits, yet the developmental and molecular mechanisms that generate this precision remain poorly understood. My recent work identified a previously unrecognized wiring strategy in which spatial information is encoded by graded synaptic connectivity within a single genetically defined neuron type, revealing a principle of within-cell-type synaptic specificity I demonstrated that these synaptic gradients are instructed by spatially graded expression of cell-recognition molecules, establishing a direct relationship between gene expression levels and the number of synapses formed with downstream targets. This work defines a quantitative mode of neuronal connectivity in which molecular gradients specify synapse number rather than binary partner choice, a principle that may generalize across neural circuits. The goal of my independent research program is to define how these within-cell-type molecular gradients are established during development and how they are translated into quantitative differences in synaptic connectivity. Building directly on my prior discoveries, my laboratory will investigate the transcriptional, regulatory, and activitydependent mechanisms that generate graded expression of cell-recognition molecules within single neuronal populations. Using the Drosophila visual system as a genetically tractable model, we will determine how developmental patterning cues and gene regulatory networks give rise to molecular gradients and test how perturbing these gradients alters synapse number, circuit function, and behavior. Together, this work will establish a developmental framework linking graded gene expression to synaptic connectivity. To assess the generality of this wiring strategy, my laboratory will extend these analyses across multiple visual circuits in the fly brain to determine whether within-cell-type molecular gradients represent a widespread mechanism for establishing quantitative differences in synaptic connectivity. In parallel, we will develop genetic tools to measure and manipulate gradients at the protein level in vivo, enabling direct tests of how gene expression levels are translated into synapse number. Finally, we will leverage comparative analyses to relate these findings to topographic gradients of gene expression observed in mammalian cortical circuits, establishing conceptual continuity between insect and vertebrate brains. Together, this work will define a broadly applicable molecular principle by which graded gene expression programs generate functional diversity within neuronal cell types and shape circuit architecture and function.


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 = $249,000 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Vision Research	000	3	5/4/2026	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

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Molecular determinants of synaptic specificity underlying a visuomotor transformation

Award Number: R00EY036123

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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