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Mechanisms and Role of Spontaneous Retinal Waves in Visual Development.

Award Number: R01EY015788
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2005
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Mechanisms and Role of Spontaneous Retinal Waves in Visual Development. - PROJECT SUMMARY Experiments in this proposal will advance our understanding of mechanisms responsible for the development of precise neural circuitry in the mammalian brain. Patterned activity is critical for normal development of neural circuits, and deficits in activity-dependent circuit refinement are associated with neurodevelopmental disorders such as Fragile X syndrome, autism, and amblyopia. Amblyopia is the most common cause of monocular visual impairment among young and middle-aged adults, with approximately 3 in 100 children effected. Amblyopia is characterized by a range of deficits in spatial vision, spatial contrast sensitivity, and other tasks. However, the mechanisms of this maladaptation are not well understood. We will employ a broad range of techniques, including molecular biological, cell biological, neuroanatomical, electrophysiological and advanced optical imaging techniques in vitro and in vivo. We focus our experiments on neural circuits in the midbrain superior colliculus and visual cortex of the mouse. Beyond the retina, these areas are the largest visual structures in the brain. The superior colliculus is a sensory motor structure that has emerged as an ideal model system for the examination of neural circuit development and function. The visual cortex is a canonical model system for the study of higher order brain function and development in mammals. It is widely hypothesized that molecular cues are responsible for the establishment of gross brain circuit features, and activity dependent processes subsequently refine these circuits to functional precision. The emergence of visual circuit features before the onset of sensory experience suggests that visual map formation is first initiated by activity-independent mechanisms, such as axon guidance molecules, then refined by pre-vision correlated spontaneous activity, and later maintained and sharpened by visual experience after eye-opening. Spontaneous bursting of retinal ganglion cells results in propagating waves of activity that change with age based on their primary excitatory drive. Initially characterized in vitro, stage I waves occur before birth and are mediated by gap junctions between retinal ganglion cells. Stage II occur from birth until around P10 and are mediated by cholinergic starburst amacrine cells. Stage III waves are glutamatergic in origin, with bipolar cells providing the primary excitatory drive onto retinal ganglion cells from P10 until eye-opening. This project aims to examine the specific spatiotemporal features and the underlying cellular mechanisms by which retinal waves are instructive for the development of higher order circuits and neuronal response properties, in both subcortical and cortical circuits, prior to eye opening.


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: 2025 ( Subtotal = $592,300 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	17	4/18/2025	NON-COMPETING CONTINUATION	$592,300
														Subtotal = $592,300

Issue Date FY: 2024 ( Subtotal = $592,300 )
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	16	1/30/2024	NON-COMPETING CONTINUATION	$592,300
														Subtotal = $592,300

Issue Date FY: 2023 ( Subtotal = $592,300 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	15	1/27/2023	NON-COMPETING CONTINUATION	$592,300
														Subtotal = $592,300

Issue Date FY: 2022 ( Subtotal = $585,600 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	14	12/14/2021	COMPETING CONTINUATION	$585,600
														Subtotal = $585,600

Issue Date FY: 2021 ( Subtotal = -$131 )
2021	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Dietary Supplement Research Program	000	13	8/21/2021	SUPPLEMENT FOR EXPANSION	-$131
														Subtotal = -$131

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	13	2/26/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $499,589 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Dietary Supplement Research Program	002	13	9/24/2018	SUPPLEMENT FOR EXPANSION	$166,589
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	13	2/5/2018	NON-COMPETING CONTINUATION	$299,700
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	001	13	6/4/2018	NON-COMPETING CONTINUATION	$33,300
														Subtotal = $499,589

Issue Date FY: 2017 ( Subtotal = $333,000 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	001	12	8/14/2017	NON-COMPETING CONTINUATION	$33,300
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Vision Research	000	12	3/13/2017	NON-COMPETING CONTINUATION	$299,700
														Subtotal = $333,000

Issue Date FY: 2016 ( Subtotal = $333,000 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	11	1/29/2016	NON-COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2015 ( Subtotal = $333,000 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	10	12/31/2014	COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2012 ( Subtotal = $673,202 )
2012	2012	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	9	6/28/2012	NON-COMPETING CONTINUATION	$393,228
2012	2012	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	001	9	9/25/2012	SUPPLEMENT FOR EXPANSION	$279,974
														Subtotal = $673,202

Issue Date FY: 2011 ( Subtotal = $393,228 )
2011	2011	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	8	6/29/2011	NON-COMPETING CONTINUATION	$393,228
														Subtotal = $393,228

Issue Date FY: 2010 ( Subtotal = $409,613 )
2010	2010	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	7	7/2/2010	NON-COMPETING CONTINUATION	$409,613
														Subtotal = $409,613

Issue Date FY: 2009 ( Subtotal = $712,990 )
2009	2009	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	001	6	7/14/2009	COMPETING CONTINUATION	$413,750
2009	2009	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Trans-NIH Recovery Act Research Support	002	6	9/23/2009	SUPPLEMENT FOR EXPANSION	$299,240
2009	2008	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	5	7/14/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $712,990

Issue Date FY: 2008 ( Subtotal = $314,904 )
2008	2008	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	5	5/9/2008	NON-COMPETING CONTINUATION	$314,904
														Subtotal = $314,904

Issue Date FY: 2007 ( Subtotal = $320,440 )
2007	2007	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Vision Research	000	4	6/5/2007	NON-COMPETING CONTINUATION	$320,440
														Subtotal = $320,440

Issue Date FY: 2006 ( Subtotal = $292,950 )
2006	2006	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	2	5/23/2006	NON-COMPETING CONTINUATION	$292,950
														Subtotal = $292,950

Issue Date FY: 2005 ( Subtotal = $300,000 )
2005	2005	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	1	7/25/2005	NEW	$300,000
														Subtotal = $300,000

Grand Total All Awards = $7,278,285

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Mechanisms and Role of Spontaneous Retinal Waves in Visual Development.

Award Number: R01EY015788

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2005

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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