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Integration of Basal Ganglia and Cerebellar Outputs in Motor Control and Parkinson's Disease

Award Number: R01NS151987
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: 09/22/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Integration of Basal Ganglia and Cerebellar Outputs in Motor Control and Parkinson's Disease - Project Summary: Parkinson’s disease (PD) is traditionally viewed as a disorder of basal ganglia (BG) dysfunction caused by dopaminergic degeneration. However, growing evidence indicates that motor impairment in PD arises from broader network-level disturbances that involve the cerebellum (CB) and thalamus. The thalamus serves as the principal convergence point for BG and CB outputs, yet how these pathways integrate at the cellular and circuit level, and how this integration fails in PD remains unknown. Our preliminary work identifies a distinct population of thalamic neurons that receives direct input from both BG and CB pathways, displays unique synaptic and molecular properties, and shows altered activity in PD models. These findings challenge classical models of strictly segregated subcortical motor circuits and suggest that BG–CB convergence may play a critical role in normal and pathological motor control. This proposal aims to define the anatomical, physiological, and disease-related mechanisms of BG/CB integration in the thalamus. Aim 1 will map the anatomical organization of BG and CB convergence using intersectional viral tracing and whole-brain reconstruction. Aim 2 will determine the synaptic and physiological rules by which inhibitory BG and excitatory CB inputs are integrated at single-neuron and population levels, leveraging dual-color optogenetics, ex vivo electrophysiology, and in vivo two-photon calcium imaging during motor learning. Aim 3 will examine how PD-induced neurodegeneration remodels thalamic inputs and firing patterns using 6-OHDA and inducible MCI-Park mouse models, and will test circuit-based rescue strategies, including targeted optogenetic deep brain stimulation, to restore balanced BG/CB influence and improve motor performance. By integrating molecular anatomy, deep-brain imaging, electrophysiology, machine-learning–based behavioral analysis, and disease modeling, this project will uncover fundamental principles of BG–CB interaction, establish how their convergence shapes motor control, and identify new circuit-level therapeutic targets for PD. Ultimately, this work reframes PD as a distributed network disorder and positions the thalamus as a key site for mechanistic insight and intervention. 1


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: 2026 ( Subtotal = $637,383 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/17/2026	NEW	$637,383
														Subtotal = $637,383

Grand Total All Awards = $637,383

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Integration of Basal Ganglia and Cerebellar Outputs in Motor Control and Parkinson's Disease

Award Number: R01NS151987

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: 09/22/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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