Project Details
Description
PROJECT SUMMARY/ABSTRACT
The goal of this proposal is to characterize the evolution of changes in neuronal activity and connectivity that
occur within and across nodal points in the basal ganglia thalamocortical (BGTC) circuit using a progressive
nonhuman primate (NHP) model of Parkinson’s disease (PD). Simultaneous recordings from populations of
neurons as well as local field potential (LFP) activity will be made from the basal ganglia, motor and sensory
thalamus, primary motor (MC) and sensory cortex (S1) as well as dorsal premotor (PMd), supplementary motor
area (SMA) and dorsolateral prefrontal (DLPFC) cortices in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) progressive model of PD. Data will be collected during both rest and movement, on and off L-dopa and
on L-dopa during drug-induced dyskinesia. A within-subject design will be used as animals progress from the
normal to mild, moderate and severe conditions of parkinsonism. Specific Aim 1 will characterize changes in
coupling and connectivity that occur between the subthalamic nucleus, internal and external segments of the
globus pallidus, motor thalamus (ventralis anterior (VA), ventralis lateralis, pars oralis (VLo), ventralis posterior
lateralis, pars oralis (VPLo), and cortical areas involved in the planning, preparation and execution of movement
(PMd, DLPFC, SMA, and MC). Specific Aim 2 will examine the effect of dopaminergic therapy (L-dopa) on
subcortical↔cortical connectivity and the relationship of these changes to improvement in motor signs and the
development of L-dopa induced dyskinesia (LID). Specific Aim 3 will characterize the changes and contribution
of altered sensorimotor processing in thalamo↔cortical and cortical↔cortical circuits (MC-S1). This proposal will
define the relationship between changes in synchronized oscillatory activity in, and effective connectivity
between, subcortical↔cortical and cortical↔cortical regions of the broader BGTC network to parkinsonian motor
signs as they develop, progress in severity, and improve with L-dopa. It will also characterize the role of changes
in different frequency spectrums to the preparation, planning and execution of movement, as well as the
contribution of sensory dysfunction in thalamocortical circuits to the motor dysfunction observed in PD. A better
understanding of the role of individual motor circuits and the types of physiological changes that occur within
these circuits and how they relate to the development of individual motor signs will provide the rationale for the
development of new targets and neuromodulation therapies directed at restoring a more normal pattern of activity
in the BGTC circuit.
Status | Active |
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Effective start/end date | 2/1/08 → 6/30/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $645,081.00
- National Institute of Neurological Disorders and Stroke: $609,589.00
- National Institute of Neurological Disorders and Stroke: $412,438.00
- National Institute of Neurological Disorders and Stroke: $535,642.00
- National Institute of Neurological Disorders and Stroke: $631,421.00
- National Institute of Neurological Disorders and Stroke: $598,998.00
- National Institute of Neurological Disorders and Stroke: $515,380.00
- National Institute of Neurological Disorders and Stroke: $629,951.00
- National Institute of Neurological Disorders and Stroke: $593,619.00
- National Institute of Neurological Disorders and Stroke: $602,477.00
- National Institute of Neurological Disorders and Stroke: $629,687.00
- National Institute of Neurological Disorders and Stroke: $594,992.00
- National Institute of Neurological Disorders and Stroke: $593,300.00
- National Institute of Neurological Disorders and Stroke: $194,274.00
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