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Characterization and connectomics of striatal interneurons

Award Number: R01NS034865
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: 02/01/1997
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Characterization and connectomics of striatal interneurons - Project Summary/Abstract The striatum is the main input structure of the basal ganglia, a system that is crucial not only for voluntary motor control, but also for reinforcement-mediated learning and higher cognitive functions. The importance of the striatum is illustrated by the severe disabilities associated with numerous neurological and neuropsy- chiatric conditions that affect this brain structure. The recent introduction of methods for targeting and manipulating genetically and physiologically defined cell types is currently revolutionizing our understanding of the neostriatum. Our preliminary studies, together with recent research demonstrate that the classically known cell types represent less than a third of the interneuron classes in the striatum, and reveal an intricate and precisely organized circuitry of these neurons. The prosed study will test 4 novel hypotheses which were formulated on the basis of preliminary data and capture functionally important principles of organization of the network of striatal interneurons. First, we will investigate the connectivity of genetically identified interneurons and test the hypotheses that their connectivity is highly cell type specific and structured to form at least 2 separate interneuron sub- networks within the neostriatum. Second, building on our previous research and novel preliminary data we hypothesize that cholinergic interneurons (CINs), which traditionally have been thought of as neuromodulatory elements, participate in a fast bi-directional synaptic network with multiple GABAergic interneurons utilizing nicotinic excitatory connections. Importantly, our preliminary data also suggest the existence of a novel source of nicotinic excitation from the brainstem that appears to selectively target a distinct subset of GABAergic interneurons. Third, we will test the hypothesis that a subset of interneurons are hierarchically organized in the sense that one or more classes of interneurons exist which are specialized to control the activity of other interneurons. These interneuron-specific interneurons are of great interest because their impact may be widely distributed and disproportionally amplified via hierarchical control of other interneurons. Finally, based on preliminary data we hypothesize that a class of novel GABAergic interneurons are essential for normal goal-directed behavior, and we will explore the mechanism of action of these neurons using in vivo electrophysiological and Ca2+-imaging methods. These experiments will yield important new insights into the functioning of the striatum and may help to identify new cellular substrates for therapeutic interventions in a variety of neurological and neuropsychiatric disorders.


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 = $0 )
2024	2022	RUTGERS, THE STATE UNIVERSITY	123 WASHINGTON ST	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	2/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $633,181 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	6/28/2022	NON-COMPETING CONTINUATION	$633,181
														Subtotal = $633,181

Issue Date FY: 2021 ( Subtotal = $633,181 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	6/29/2021	NON-COMPETING CONTINUATION	$633,181
														Subtotal = $633,181

Issue Date FY: 2020 ( Subtotal = $633,181 )
2020	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	7/8/2020	NON-COMPETING CONTINUATION	$633,181
														Subtotal = $633,181

Issue Date FY: 2019 ( Subtotal = $601,212 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	21	7/5/2019	NON-COMPETING CONTINUATION	$601,212
2019	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	1/10/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $601,212

Issue Date FY: 2018 ( Subtotal = $581,751 )
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	20	9/18/2018	COMPETING CONTINUATION	$0
2018	2018	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	1/9/2018	COMPETING CONTINUATION	$581,751
														Subtotal = $581,751

Issue Date FY: 2017 ( Subtotal = $546,055 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	7/21/2017	NON-COMPETING CONTINUATION	$546,055
2017	2015	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	123 WASHINGTON ST STE 510	NEWARK	NJ	07102	ESSEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	1/17/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $546,055

Issue Date FY: 2016 ( Subtotal = $590,738 )
2016	2016	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	9/7/2016	SUPPLEMENT FOR EXPANSION	$50,000
2016	2016	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	7/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$540,738
														Subtotal = $590,738

Issue Date FY: 2015 ( Subtotal = $535,817 )
2015	2015	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	7/21/2015	NON-COMPETING CONTINUATION	$535,817
														Subtotal = $535,817

Issue Date FY: 2014 ( Subtotal = $525,950 )
2014	2014	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	7/10/2014	NON-COMPETING CONTINUATION	$525,950
2014	2012	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	9/26/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $525,950

Issue Date FY: 2013 ( Subtotal = $527,041 )
2013	2013	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	9/25/2013	COMPETING CONTINUATION	$527,041
														Subtotal = $527,041

Issue Date FY: 2012 ( Subtotal = $331,209 )
2012	2012	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	6/28/2012	NON-COMPETING CONTINUATION	$331,209
														Subtotal = $331,209

Issue Date FY: 2011 ( Subtotal = $331,209 )
2011	2011	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	6/24/2011	NON-COMPETING CONTINUATION	$331,209
														Subtotal = $331,209

Issue Date FY: 2010 ( Subtotal = $398,090 )
2010	2010	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	6/18/2010	NON-COMPETING CONTINUATION	$334,590
2010	2010	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	8/23/2010	SUPPLEMENT FOR EXPANSION	$63,500
														Subtotal = $398,090

Issue Date FY: 2009 ( Subtotal = $337,969 )
2009	2009	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	6/30/2009	COMPETING CONTINUATION	$337,969
														Subtotal = $337,969

Issue Date FY: 2007 ( Subtotal = $315,158 )
2007	2007	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	3/28/2007	NON-COMPETING CONTINUATION	$315,158
														Subtotal = $315,158

Issue Date FY: 2006 ( Subtotal = $324,570 )
2006	2006	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	4/14/2006	NON-COMPETING CONTINUATION	$324,570
														Subtotal = $324,570

Issue Date FY: 2005 ( Subtotal = $332,381 )
2005	2005	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	2/18/2005	NON-COMPETING CONTINUATION	$332,381
														Subtotal = $332,381

Issue Date FY: 2004 ( Subtotal = $332,381 )
2004	2004	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	3/1/2004	NON-COMPETING CONTINUATION	$332,381
														Subtotal = $332,381

Issue Date FY: 2003 ( Subtotal = $351,605 )
2003	2003	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6		COMPETING CONTINUATION	$351,605
														Subtotal = $351,605

Issue Date FY: 2001 ( Subtotal = $202,518 )
2001	2001	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/11/2001	NON-COMPETING CONTINUATION	$202,518
														Subtotal = $202,518

Issue Date FY: 2000 ( Subtotal = $246,621 ) (Continued on the next page)
2000	2000	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biological Basis Research in the Neurosciences	001	4	7/3/2000	SUPPLEMENT FOR EXPANSION	$50,000
Grand Total All Awards = $9,688,641

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Characterization and connectomics of striatal interneurons

Award Number: R01NS034865

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: 02/01/1997

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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