Project #3 (PI: Yoland Smith, PhD)

The loss of midbrain dopamine neurons in Parkinson’s disease (PD) induces complex anatomical and functional changes throughout the basal ganglia-thalamocortical circuitry and downstream targets. Although our understanding of PD-related neuronal activity changes in basal ganglia nuclei has increased significantly over the past decades, much remains to be known about the pathophysiology of the motor cortex in parkinsonism. In this project, we will use a viral vector approach to identify corticospinal neurons in the primary and supplementary motor cortices and determine if these neurons undergo neuropathological changes of their dendritic arbors and axonal projections in the MPTP-treated nonhuman primate model of Parkinson’s disease. We will also use high-resolution electron microscopic methods to examine ultrastructural changes in their synaptic innervation. Together, results of this project will determine if the corticospinal neurons, the main source of motor commands to the spinal cord, are a major target of Parkinson’s disease pathology. Such information is critical to our understanding of the pathophysiology of the basal ganglia-thalamocortical loops in parkinsonism and for the development of future neuromodulation therapies aimed at specific populations of motor cortical neurons in PD.