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Lesion and Activity Dependent Corticospinal Tract Plasticity

Award Number: R01NS064004
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: 05/19/2009
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Lesion and Activity Dependent Corticospinal Tract Plasticity - Corticospinal tract (CST) injury deprives spinal circuits of movement control signals. This leads to loss of function—muscle weakness and paralysis—and gain of dysfunction—including hyperreflexia and spasticity. To repair the CST after injury and restore motor control, it is necessary to abrogate the impairments due to both the loss of function and gain of dysfunction following injury. Our research during the prior funding period shows that activity-dependent processes underlie both the loss of function and gain of dysfunction after CST injury. This finding provides the foundation for developing new therapeutic neuromodulatory approaches to target activity dependence using motor cortex (MCX) stimulation and transspinal direct current stimulation (tsDCS). MCX stimulation after injury is effective in CST repair and motor recovery. In Aim 1 we will determine the most effective MCX neuromodulation treatment to produce persistent structural and functional plasticity of the corticospinal system. Using different stimulation patterns, we will ask if efficacy depends on recruiting CST axon growth-promoting signaling. Using optogenetics to identify activated CST axons, we will test how stimulation patterns determine anatomical and physiological outcomes. Knowing that recovery is more than CST sprouting, we will ask if efficacy depends on producing long-term physiological changes in spinal circuits. We recently showed that selective CST injury or MCX inactivation produces trans-neuronal loss of spinal cholinergic interneurons and that this loss can be rescued by spinal activation. In Aim 2 we will determine how MCX neuromodulation regulates transneuronal segmental circuit remodeling after injury to promote spinal circuit repair. We will ask how CST injury impacts the major class of excitatory premotor interneurons of the CST. We will test if MCX stimulation ameliorates trans-neuronal circuit changes and then examine the interplay of repair strategies differentially targeting microglial-based spinal circuit remodeling and CST sprouting In Aim 3 we will harness the differential actions of tsDCS on spinal circuits to enhance repair and rehabilitation efficacy after cervical SCI. Spinal circuits integrate motor control signals with afferent information. After SCI, with the loss of motor pathways, spared afferent feedback dominates segmental circuit function. We recently showed that afferent competition diminishes CST connection strength, to reinforce afferent over integrated control. We will use the differential actions of tsDCS to promote spared CST function and weaken potentially “runaway” afferent input, to rebalance segmental control. We will develop a novel strategy that combines neuromodulation-based repair with neuromodulation-assisted rehabilitation to promote recovery. Successful completion of our studies will advance our understanding of the mechanisms of impairment and the mechanisms underlying novel neuromodulatory repair strategies after SCI. Results will inform how best to integrate motor behavioral rehabilitation and activity-based interventions to provide potentially clinically relevant approaches to improve motor control in humans after cervical SCI.


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 = $0 )
2025	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	8/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $343,438 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	5/31/2023	NON-COMPETING CONTINUATION	$343,438
														Subtotal = $343,438

Issue Date FY: 2022 ( Subtotal = $386,391 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	6/9/2022	SUPPLEMENT FOR EXPANSION	$42,953
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	6/8/2022	NON-COMPETING CONTINUATION	$343,438
														Subtotal = $386,391

Issue Date FY: 2021 ( Subtotal = $447,755 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	13	6/17/2021	NON-COMPETING CONTINUATION	-$73,635
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	13	6/17/2021	SUPPLEMENT FOR EXPANSION	$73,635
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	13	5/26/2021	NON-COMPETING CONTINUATION	$417,073
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	5/17/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	4/23/2021	SUPPLEMENT FOR EXPANSION	$30,682
														Subtotal = $447,755

Issue Date FY: 2020 ( Subtotal = $338,450 )
2020	2020	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	12	6/1/2020	NON-COMPETING CONTINUATION	$338,450
2020	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	11	1/31/2020	COMPETING CONTINUATION	$24,562
2020	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	11	2/20/2020	COMPETING CONTINUATION	$0
2020	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	1/31/2020	NON-COMPETING CONTINUATION	-$24,562
2020	2016	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/30/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $338,450

Issue Date FY: 2019 ( Subtotal = $335,458 )
2019	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	11	6/25/2019	COMPETING CONTINUATION	$335,458
2019	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/21/2019	NON-COMPETING CONTINUATION	$0
2019	2015	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	6/24/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $335,458

Issue Date FY: 2017 ( Subtotal = $334,688 )
2017	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	8/9/2017	NON-COMPETING CONTINUATION	$334,688
2017	2016	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/11/2017	EXTENSION WITH OR WITHOUT FUNDS	$42,179
2017	2015	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/11/2017	NON-COMPETING CONTINUATION	-$42,179
														Subtotal = $334,688

Issue Date FY: 2016 ( Subtotal = $334,688 )
2016	2016	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	8/31/2016	EXTENSION WITH OR WITHOUT FUNDS	$334,688
														Subtotal = $334,688

Issue Date FY: 2015 ( Subtotal = $334,688 )
2015	2015	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	7/28/2015	NON-COMPETING CONTINUATION	$334,688
														Subtotal = $334,688

Issue Date FY: 2014 ( Subtotal = $331,340 )
2014	2014	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	8/1/2014	NON-COMPETING CONTINUATION	$331,340
														Subtotal = $331,340

Issue Date FY: 2013 ( Subtotal = $334,688 )
2013	2013	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	9/16/2013	COMPETING CONTINUATION	$334,688
2013	2012	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	9/13/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $334,688

Issue Date FY: 2012 ( Subtotal = $364,532 )
2012	2012	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/23/2012	NON-COMPETING CONTINUATION	$364,532
														Subtotal = $364,532

Issue Date FY: 2011 ( Subtotal = $363,529 )
2011	2011	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/1/2011	NON-COMPETING CONTINUATION	$333,854
2011	2011	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/14/2011	NON-COMPETING CONTINUATION	$29,675
														Subtotal = $363,529

Issue Date FY: 2010 ( Subtotal = $366,258 )
2010	2010	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	3/23/2010	NON-COMPETING CONTINUATION	$366,258
2010	2009	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW Memorial LIBRARY	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/17/2009	NEW	-$320,474
2010	2009	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	12/21/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$320,474
														Subtotal = $366,258

Issue Date FY: 2009 ( Subtotal = $345,242 )
2009	2009	COLUMBIA UNIVERSITY, SCHOOL OF ARTS & SCIENCES	106 LOW Memorial LIBRARY	NEW YORK	NY	10027	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/15/2009	NEW	$345,242
														Subtotal = $345,242

Grand Total All Awards = $4,961,145

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Lesion and Activity Dependent Corticospinal Tract Plasticity

Award Number: R01NS064004

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: 05/19/2009

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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