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Pacemakers of Cholinergic Wave Activity in the Developing Retina

Award Number: R15EY034305
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Pacemakers of Cholinergic Wave Activity in the Developing Retina - PROJECT SUMMARY Before the emergence of vision, spontaneous retinal wave activity is essential for retinal layer-specific angiogenesis and dendritic maturation of retinal ganglion cells, as well as for the refinement of eye-specific segregations and retinotopic maps. A subpopulation of retinal amacrine interneurons, called starburst amacrine cells, initiate and propagate retinal waves through recurrent cholinergic connections called cholinergic retinal waves. However, the mechanisms underlying cholinergic wave initiation and propagation are poorly defined. Currently, the most urgent priority is to define how cholinergic waves are initiated to create a framework for understanding their downstream propagation. This project's objective is to identify a subset of starburst amacrine cells that serve as cholinergic wave pacemakers and the mechanisms by which pacemaker starburst amacrine cells generate these waves. Preliminary data from the PI's laboratory demonstrate that it is feasible to identify pacemaker starburst amacrine cells and the sufficiency of a single pacemaker starburst amacrine cell to initiate a wave. Wave generation requires activation of voltage-dependent calcium channels. These novel findings lead to the central hypothesis: single pacemaker starburst amacrine cells initiate waves by a calcium-dependent mechanism. To test this hypothesis, the team will determine the distribution and properties of cholinergic wave pacemakers (Aim 1), and identify the calcium-dependent mechanisms of cholinergic wave generation (Aim 2). The work on understanding the identity and features of pacemaker starburst amacrine cells and the ionic mechanisms of cholinergic retinal wave generation will advance knowledge of how retinal waves mediate vascular and neuronal development of the retina as well as eye-specific segregation and retinotopic map refinement in the visual centers of the brain.


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	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Vision Research	000	1	8/11/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $429,016 )
2023	2023	OAKLAND UNIVERSITY	2200 N SQUIRREL RD	ROCHESTER	MI	48309	OAKLAND	USA	Vision Research	000	1	8/29/2023	NEW	$429,016
														Subtotal = $429,016

Grand Total All Awards = $429,016

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Pacemakers of Cholinergic Wave Activity in the Developing Retina

Award Number: R15EY034305

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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