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Neuron- and Circuit-Specific Mechanisms and Adaptations Regulating Motor Function in Parkinson Disease Models

Award Number: R01NS064984
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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ABSTRACT Parkinson's disease (PD) is the second most common neurodegenerative disease (after Alzheimer's disease), afflicting tens of millions worldwide. The characteristic disease symptoms arise from basal ganglia dysfunction that occurs secondary to loss of dopamine neurons in the substantia nigra pars compacta. Symptomatic treatment is focused either on replacing dopamine or disrupting aberrant activity through deep- brain stimulation in the subthalamic nucleus or the primary basal ganglia output nucleus in the primate, internal globus pallidus (GPi). This proposal is aimed at understanding the function and dysfunction of basal ganglia circuitry in mice, at the output of the basal ganglia to motor thalamus. In Aim 1, we will develop strategies to identify basal ganglia-recipient motor thalamus neurons in ventral anterior/ventral lateral thalamus (VA/VL), and characterize their projection targets and cortical inputs in awake, behaving animals. In Aim 2, we will use sophisticated in vivo strategies to record from posterior EP neurons and VA/VL neurons as animals move their limbs during locomotion, a fixed repetitive behavior. We will perturb activity in this pathway using optogenetics to determine the contribution of activity in these neurons to forelimb movements, and we will examine how activity in this pathway is altered after loss of striatal dopamine. In Aim 3, we will perform similar experiments in mice performing a lever-pulling task, a flexible forelimb movement. We will examine both cued and uncued versions of this task to distinguish activity generated internally vs. externally. Finally, we will examine how loss of striatal dopamine impacts EP and VA/VL activity during flexible forelimb movements. Our overarching goal is to understand how loss of striatal dopamine in PD leads to disruptions in basal ganglia circuit function and motor deficits, in order to develop novel therapeutic strategies for treating PD motor symptoms.


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: 2023 ( Subtotal = -$404,962 )
2023	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	7/5/2023	NON-COMPETING CONTINUATION	-$1
2023	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	1/9/2023	NON-COMPETING CONTINUATION	-$404,961
														Subtotal = -$404,962

Issue Date FY: 2022 ( Subtotal = $468,551 )
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	4/19/2022	NON-COMPETING CONTINUATION	$468,551
														Subtotal = $468,551

Issue Date FY: 2021 ( Subtotal = $468,551 )
2021	2021	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	5/13/2021	NON-COMPETING CONTINUATION	$468,551
														Subtotal = $468,551

Issue Date FY: 2020 ( Subtotal = $468,551 )
2020	2020	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	1/31/2020	COMPETING CONTINUATION	$468,551
2020	2018	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	2/19/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $468,551

Issue Date FY: 2018 ( Subtotal = $417,813 )
2018	2018	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	7/30/2018	NON-COMPETING CONTINUATION	$417,813
														Subtotal = $417,813

Issue Date FY: 2017 ( Subtotal = $417,813 )
2017	2017	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	8/29/2017	NON-COMPETING CONTINUATION	$417,813
														Subtotal = $417,813

Issue Date FY: 2016 ( Subtotal = $417,813 )
2016	2016	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	8/30/2016	NON-COMPETING CONTINUATION	$417,813
														Subtotal = $417,813

Issue Date FY: 2015 ( Subtotal = $417,813 )
2015	2015	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	7/21/2015	NON-COMPETING CONTINUATION	$417,813
														Subtotal = $417,813

Issue Date FY: 2014 ( Subtotal = $417,813 )
2014	2014	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	8/18/2014	COMPETING CONTINUATION	$417,813
														Subtotal = $417,813

Issue Date FY: 2013 ( Subtotal = $395,126 )
2013	2013	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/2/2013	NON-COMPETING CONTINUATION	$368,512
2013	2013	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/21/2013	NON-COMPETING CONTINUATION	$26,614
														Subtotal = $395,126

Issue Date FY: 2012 ( Subtotal = $409,456 )
2012	2012	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/29/2012	NON-COMPETING CONTINUATION	$409,456
														Subtotal = $409,456

Issue Date FY: 2011 ( Subtotal = $409,456 )
2011	2011	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	6/2/2011	NON-COMPETING CONTINUATION	$33,425
2011	2011	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/18/2011	NON-COMPETING CONTINUATION	$376,031
														Subtotal = $409,456

Issue Date FY: 2010 ( Subtotal = $413,635 )
2010	2010	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/14/2010	NON-COMPETING CONTINUATION	$413,635
														Subtotal = $413,635

Issue Date FY: 2009 ( Subtotal = $417,813 )
2009	2009	J DAVID GLADSTONE INSTITUTES	P.O. BOX 419100	SAN FRANCISCO	CA	94141	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/29/2009	NEW	$417,813
														Subtotal = $417,813

Grand Total All Awards = $5,135,242

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Neuron- and Circuit-Specific Mechanisms and Adaptations Regulating Motor Function in Parkinson Disease Models

Award Number: R01NS064984

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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