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Physiology of Single Synaptic CNS Terminals

Award Number: R01NS036942
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Physiology of Single Synaptic CNS Terminals - Abstract Mammalian brains are extremely sensitive to metabolic perturbation. If blood glucose drops by only a factor of ~2, immediate neurological symptoms emerge, including delirium and coma. We identified nerve terminals as a one of the likely loci of this vulnerability, as the vesicle recycling program crashes very quickly upon fuel withdrawal. We hypothesize that this metabolic sensitivity may lie at the heart of both neurodegenerative and neuropsychiatric diseases, as brain hypometabolism is a strong predictor of the onset of these diseases (albeit on different time scales). We seek to address many fundamental knowledge gaps we have concerning how local synaptic metabolism is regulated, including what molecular machineries for metabolism support synapse function and how different metabolic fuels can be used to support synapse function. We recently determined that one of the ten enzymes needed for glycolysis serves as a critical control point for glycolytic flux in nerve terminals. Enhancing the activity of his enzyme, PGK-1, only 2-fold is sufficient to provide dramatic protection against hypometabolic synaptic dysfunction. We recently discovered that synapses contain the necessary machinery to both synthesize and utilize lipid droplets, and that they normally constantly burn through these lipid droplets to sustain synapse function. Mutations in the key triglyceride lipase required to lipid droplet use are drivers of neurological disease, including intellectual disability. Similarly, we have recently uncovered a new role for neuromodulators at nerve terminals: in addition to directly controlling synapse function, they serve as signals to tell synapses to either store or use glycogen. Our aims to examine how difference cell biological machineries in synapses allow fuel switching and how perturbations in these machineries drive or heighten neurological disease states.


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 = $444,432 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	26	2/13/2025	NON-COMPETING CONTINUATION	$444,432
														Subtotal = $444,432

Issue Date FY: 2024 ( Subtotal = $503,022 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	1/18/2024	COMPETING CONTINUATION	$493,813
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	25	8/12/2024	COMPETING CONTINUATION	$9,209
														Subtotal = $503,022

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	2/25/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $365,991 )
2014	2014	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	5/2/2014	NON-COMPETING CONTINUATION	$365,991
														Subtotal = $365,991

Issue Date FY: 2013 ( Subtotal = $356,749 )
2013	2013	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	5/24/2013	NON-COMPETING CONTINUATION	$24,030
2013	2013	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	5/2/2013	NON-COMPETING CONTINUATION	$332,719
														Subtotal = $356,749

Issue Date FY: 2012 ( Subtotal = $369,688 )
2012	2012	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	5/7/2012	NON-COMPETING CONTINUATION	$369,688
														Subtotal = $369,688

Issue Date FY: 2011 ( Subtotal = $369,688 )
2011	2011	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	5/31/2011	COMPETING CONTINUATION	$369,688
2011	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/27/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $369,688

Issue Date FY: 2010 ( Subtotal = $363,826 )
2010	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	11/20/2009	NON-COMPETING CONTINUATION	$330,750
2010	2010	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	1/19/2010	NON-COMPETING CONTINUATION	$33,076
														Subtotal = $363,826

Issue Date FY: 2009 ( Subtotal = $400,500 )
2009	2009	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	11/20/2008	NON-COMPETING CONTINUATION	$330,750
2009	2009	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	12	8/26/2009	SUPPLEMENT FOR EXPANSION	$33,000
2009	2009	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK	NY	10021	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	4/7/2009	NON-COMPETING CONTINUATION	$36,750
														Subtotal = $400,500

Issue Date FY: 2008 ( Subtotal = $367,500 )
2008	2008	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	12/4/2007	NON-COMPETING CONTINUATION	$367,500
														Subtotal = $367,500

Issue Date FY: 2007 ( Subtotal = $367,500 )
2007	2007	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/24/2007	COMPETING CONTINUATION	$367,500
														Subtotal = $367,500

Issue Date FY: 2006 ( Subtotal = $353,792 )
2006	2006	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/27/2006	NON-COMPETING CONTINUATION	$353,792
														Subtotal = $353,792

Issue Date FY: 2005 ( Subtotal = $362,306 )
2005	2005	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/3/2004	NON-COMPETING CONTINUATION	$362,306
														Subtotal = $362,306

Issue Date FY: 2004 ( Subtotal = $362,306 )
2004	2004	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	12/5/2003	NON-COMPETING CONTINUATION	$362,306
														Subtotal = $362,306

Issue Date FY: 2003 ( Subtotal = $362,306 )
2003	2003	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6		NON-COMPETING CONTINUATION	$362,306
														Subtotal = $362,306

Issue Date FY: 2002 ( Subtotal = $362,306 )
2002	2002	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/14/2001	COMPETING CONTINUATION	$362,306
														Subtotal = $362,306

Issue Date FY: 2001 ( Subtotal = $277,507 )
2001	2001	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/27/2001	NON-COMPETING CONTINUATION	$277,507
														Subtotal = $277,507

Issue Date FY: 2000 ( Subtotal = $269,423 )
2000	2000	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Biological Basis Research in the Neurosciences	000	3	12/6/1999	NON-COMPETING CONTINUATION	$269,423
														Subtotal = $269,423

Issue Date FY: 1999 ( Subtotal = $261,576 )
1999	1999	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Biological Basis Research in the Neurosciences	000	2	11/27/1998	NON-COMPETING CONTINUATION	$261,576
														Subtotal = $261,576

Issue Date FY: 1998 ( Subtotal = $249,102 )
1998	1998	CORNELL UNIVERSITY, MEDICAL COLLEGE	1300 YORK AVENUE, S 217	NEW YORK-NEW YORK	NY	10021		USA	Biological Basis Research in the Neurosciences	000	1	11/25/1997	NEW	$249,102
														Subtotal = $249,102

Grand Total All Awards = $6,769,520

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Physiology of Single Synaptic CNS Terminals

Award Number: R01NS036942

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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