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Functional Roles of Retinal Gap Junctions in Visual Processing

Award Number: R01EY007360
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/1988
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Functional Roles of Retinal Gap Junctions in Visual Processing - Electrical synaptic transmission via gap junctions (GJs) is an important mode of neuronal communication in the CNS. An elegant example is the retina in which each of the five main neuronal types is electrically coupled via GJs. The broad distribution, diverse connexin subunit structure, and regulation of retinal GJs suggest a diversity of functional roles in visual processing; elucidating these roles forms the long-term goal of our experimental program. Here we propose to study the GJs in the inner mouse retina, which subserve a rich and complex variety of electrical circuits. The first aim of this proposal is to determine the role of cell-to-cell vs. neuron ensemble interactions in creating the robust, correlated activity displayed by retinal ganglion cells (RGCs). Correlated RGC activity is believed to have a number of functions, including enhancement of signal saliency and encoding of specific information about visual stimuli such as intensity, size, and motion. While it is now clear that GJs are critical to the creation of the robust concerted activity between RGC neighbors, the exact mechanism remains unclear. While it has been posited that reciprocal drive between coupled RGC neighbors can produce concerted firing, our preliminary data suggest that this does not occur. Rather, it appears that coherent activity within neuronal ensembles is necessary to recruit additional RGCs and produce their coherent activity. We propose a multidisciplinary approach combining electrophysiological, pharmacological, and optogenetic techniques applied to transgenic and knockout mouse lines to differentiate the circuits responsible for correlated RGC activity. The second aim will focus on the coupling between RGCs and amacrine cells (ACs). This type of electrical coupling occurs extensively across the retina, but how this affects neuronal activity has not been studied comprehensively due to a lack of an experimental platform to visualize and target coupled RGC-AC pairs for recording. We will target coupled RGC-AC pairs using two techniques: (1) labeling cells with the GJ-permenat dye Po-Pro-1; and (2) using the transgenic Grik4 mouse line in which ON α-RGCs and coupled ACs express fluorescent markers. For both, we will record from coupled pairs of RGCs and ACs to determine the role that this electrical interaction has on the response activity of inner retinal neurons. In the third aim we will study the novel idea that RGCs can alter intraretinal activity by signaling back to AC through interconnecting GJs. We posit that RGCs can alter the activity of coupled ACs, which, in turn, inhibit other ganglion cells via conventional chemical synapses. This form of intraretinal signaling thereby creates a circuit providing a novel form of lateral inhibition. Deficits in GJ communication have been implicated in a number of brain neuropathies, including visual impairments associated with retinitis pigmentosa, glaucoma and ischemic retinopathy. The experimental program proposed here will extend our understanding of the distribution and physiological roles of GJs, which forms an important prerequisite for determining how GJ dysfunction affects neural function so as to indicate novel targets for the treatment of human diseases.


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: 2024 ( Subtotal = -$1,019 )
2024	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	33 W 42ND STREET FL 19	NEW YORK	NY	10036	NEW YORK	USA	Vision Research	000	32	7/24/2024	NON-COMPETING CONTINUATION	-$1,019
														Subtotal = -$1,019

Issue Date FY: 2021 ( Subtotal = $392,850 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	33 W 42ND STREET FL 19	NEW YORK	NY	10036	NEW YORK	USA	Vision Research	000	32	8/20/2021	NON-COMPETING CONTINUATION	$392,850
														Subtotal = $392,850

Issue Date FY: 2020 ( Subtotal = $405,000 )
2020	2020	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	33 W 42ND STREET FL 19	NEW YORK	NY	10036	NEW YORK	USA	Vision Research	000	31	8/14/2020	NON-COMPETING CONTINUATION	$405,000
														Subtotal = $405,000

Issue Date FY: 2019 ( Subtotal = $400,027 )
2019	2019	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	33 W 42ND STREET FL 19	NEW YORK	NY	10036	NEW YORK	USA	Vision Research	000	30	9/16/2019	COMPETING CONTINUATION	$400,027
														Subtotal = $400,027

Issue Date FY: 2018 ( Subtotal = -$215 )
2018	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	33 W 42ND STREET FL 19	NEW YORK	NY	10036	NEW YORK	USA	Vision Research	000	29	7/25/2018	EXTENSION WITH OR WITHOUT FUNDS	-$215
														Subtotal = -$215

Issue Date FY: 2016 ( Subtotal = $636,274 )
2016	2016	SUNY, COLLEGE OF OPTOMETRY	122 EAST 25TH STREET	NEW YORK-NEW YORK	NY	10010		USA	Vision Research	000	29	6/28/2016	EXTENSION WITH OR WITHOUT FUNDS	$636,274
														Subtotal = $636,274

Issue Date FY: 2015 ( Subtotal = $623,547 )
2015	2015	SUNY, COLLEGE OF OPTOMETRY	122 EAST 25TH STREET	NEW YORK-NEW YORK	NY	10010		USA	Vision Research	000	28	5/14/2015	NON-COMPETING CONTINUATION	$623,547
														Subtotal = $623,547

Issue Date FY: 2014 ( Subtotal = $623,548 )
2014	2014	SUNY, COLLEGE OF OPTOMETRY	122 EAST 25TH STREET	NEW YORK-NEW YORK	NY	10010		USA	Vision Research	000	27	5/15/2014	NON-COMPETING CONTINUATION	$623,548
														Subtotal = $623,548

Issue Date FY: 2013 ( Subtotal = $646,274 )
2013	2013	SUNY, COLLEGE OF OPTOMETRY	122 EAST 25TH STREET	NEW YORK-NEW YORK	NY	10010		USA	Vision Research	001	26	4/25/2013	COMPETING CONTINUATION	$646,274
2013	2012	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	25	4/22/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $646,274

Issue Date FY: 2012 ( Subtotal = $552,670 )
2012	2012	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	25	3/6/2012	NON-COMPETING CONTINUATION	$552,670
														Subtotal = $552,670

Issue Date FY: 2011 ( Subtotal = $552,670 )
2011	2011	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	001	24	5/18/2011	NON-COMPETING CONTINUATION	$34,541
2011	2011	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	24	3/7/2011	NON-COMPETING CONTINUATION	$518,129
														Subtotal = $552,670

Issue Date FY: 2010 ( Subtotal = $558,931 )
2010	2010	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	23	2/24/2010	NON-COMPETING CONTINUATION	$558,931
														Subtotal = $558,931

Issue Date FY: 2009 ( Subtotal = $548,132 )
2009	2009	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	22	4/9/2009	NON-COMPETING CONTINUATION	$548,132
														Subtotal = $548,132

Issue Date FY: 2008 ( Subtotal = $582,298 )
2008	2008	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	21	4/1/2008	COMPETING CONTINUATION	$582,298
														Subtotal = $582,298

Issue Date FY: 2007 ( Subtotal = $487,354 )
2007	2007	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	20	3/15/2007	NON-COMPETING CONTINUATION	$487,354
														Subtotal = $487,354

Issue Date FY: 2006 ( Subtotal = $475,823 )
2006	2006	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	19	2/22/2006	NON-COMPETING CONTINUATION	$475,823
														Subtotal = $475,823

Issue Date FY: 2005 ( Subtotal = $473,082 )
2005	2005	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	18	2/28/2005	NON-COMPETING CONTINUATION	$473,082
														Subtotal = $473,082

Issue Date FY: 2004 ( Subtotal = $459,301 )
2004	2004	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	17	2/25/2004	NON-COMPETING CONTINUATION	$459,301
														Subtotal = $459,301

Issue Date FY: 2003 ( Subtotal = $489,864 )
2003	2003	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	16		COMPETING CONTINUATION	$489,864
														Subtotal = $489,864

Issue Date FY: 2002 ( Subtotal = $322,115 )
2002	2002	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	15	2/28/2002	NON-COMPETING CONTINUATION	$322,115
														Subtotal = $322,115

Issue Date FY: 2001 ( Subtotal = $312,830 )
2001	2001	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	14	3/12/2001	NON-COMPETING CONTINUATION	$312,830
														Subtotal = $312,830

Issue Date FY: 2000 ( Subtotal = $303,816 )
2000	2000	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	13	3/14/2000	NON-COMPETING CONTINUATION	$303,816
														Subtotal = $303,816

Issue Date FY: 1999 ( Subtotal = $295,063 )
1999	1999	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	12	6/18/1999	NON-COMPETING CONTINUATION	$295,063
														Subtotal = $295,063

Issue Date FY: 1998 ( Subtotal = $302,265 )
1998	1998	NEW YORK UNIVERSITY MEDICAL CENTER	550 1ST AVE, SC-2 KIPS BAY BG	NEW YORK	NY	10016	NEW YORK	USA	Vision Research	000	11	2/17/1998	COMPETING CONTINUATION	$302,265
														Subtotal = $302,265

Grand Total All Awards = $10,442,500

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Functional Roles of Retinal Gap Junctions in Visual Processing

Award Number: R01EY007360

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/1988

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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