Wednesday, July 2, 2025 7/2/2025

Striatal Mechanisms of Dyskinesia and Impulse Control in Parkinson’s Disease

Award Number: R01NS101354
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: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Striatal Mechanisms of Dyskinesia and Impulse Control in Parkinson’s Disease - Project Abstract The motor symptoms of Parkinson’s Disease (PD) are frequently treated with dopamine replacement therapies, such as the dopamine precursor levodopa or dopamine receptor agonists. While very effective for some of the cardinal motor features, these medications can cause two major complications: levodopa-induced dyskinesia (LID) and impulse control disorder (ICD). LID consists of drug-induced abnormal involuntary movements, and is closely associated with levodopa. ICD manifests as a syndrome of impulsive and/or compulsive behaviors, such as pathological gambling, hypersexuality, or binge eating, and is closely associated with dopamine D2/3R agonists. Little is known about the synaptic or circuit mechanisms of either disorder, though substantial progress has been made on LID through the use of animal models of PD/LID. In our prior work, we have found that a subset of striatal direct pathway medium spiny neurons achieve high levodopa-evoked firing rates in vivo, which correlate with and cause dyskinesia in the mouse model. Other intermingled direct pathway neurons correlate with the therapeutic effects of levodopa. We have also recently developed a mouse model of PD/ICD, based on a delay discounting task and administration of the dopamine agonist pramipexole, which will permit more mechanistic studies. In this proposal we will explore some cellular and circuit mechanisms of LID and ICD, using in vivo and ex vivo electrophysiology, optogenetics, and chemogenetics in mouse models. This proposal aims to (1) test whether local striatal inhibitory synapses are altered in and contribute to LID, (2) determine whether extrinsic inhibitory synapses from the globus pallidus to the striatum are altered in and contribute to LID, and (3) begin to explore the striatal mechanisms of ICD. These studies will build on our prior work in LID to unravel its cellular mechanisms, but also determine if ICD is mediated by similar or distinct processes. Together, these studies will lay the groundwork for new PD treatments that harness the benefits of dopamine without the complications.


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 = $398,003 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	5/22/2025	NON-COMPETING CONTINUATION	$398,003
2025	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	2/12/2025	COMPETING CONTINUATION	$41,444
2025	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/12/2025	NON-COMPETING CONTINUATION	-$41,444
														Subtotal = $398,003

Issue Date FY: 2024 ( Subtotal = $391,638 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	4/5/2024	NON-COMPETING CONTINUATION	$391,638
														Subtotal = $391,638

Issue Date FY: 2023 ( Subtotal = $398,618 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	7/6/2023	COMPETING CONTINUATION	$398,618
														Subtotal = $398,618

Issue Date FY: 2022 ( Subtotal = $444,125 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/21/2022	SUPPLEMENT FOR EXPANSION	$161,500
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/30/2022	NON-COMPETING CONTINUATION	$282,625
														Subtotal = $444,125

Issue Date FY: 2021 ( Subtotal = $282,625 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/20/2021	NON-COMPETING CONTINUATION	$282,625
														Subtotal = $282,625

Issue Date FY: 2020 ( Subtotal = $370,788 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/4/2020	NON-COMPETING CONTINUATION	$282,625
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/10/2020	SUPPLEMENT FOR EXPANSION	$88,163
														Subtotal = $370,788

Issue Date FY: 2019 ( Subtotal = $315,984 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/10/2019	NON-COMPETING CONTINUATION	$315,984
														Subtotal = $315,984

Issue Date FY: 2018 ( Subtotal = $315,000 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/2/2018	NEW	$2,953
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/8/2018	NEW	$312,047
														Subtotal = $315,000

Grand Total All Awards = $2,916,781

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Striatal Mechanisms of Dyskinesia and Impulse Control in Parkinson’s Disease

Award Number: R01NS101354

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: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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