Morris K. Udall Centers of Excellence for Parkinson's Disease Research at Emory University

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Project Summary – Overall Center The Morris K. Udall Parkinson's Disease Center of Excellence for Parkinson’s Disease Research at Emory University is a collaborative research program that studies the pathophysiology of parkinsonism with the goal of optimizing the treatment for Parkinson’s disease (PD). The Center draws upon the proven ability of the basal ganglia research community at Emory to conduct collaborative translational research. Other Udall Center assets are the availability of primates for research at the Yerkes National Primate Research Center at Emory, and the presence of one of the largest movement disorders clinic in the US. The Center consists of four projects and three cores. The planned research will shed light on the poorly understood parkinsonism-related activity changes of specifically identified groups of projection neurons in the cerebral cortex which, in turn, will help us to better understand the pathophysiology of parkinsonism, and to optimize therapeutic strategies. Project 1 (led by Dr. Jaeger) will utilize rodent experiments for large-scale voltage imaging and brain slice recordings and use neural computational approaches to develop mechanistic models of cortical dysfunction in parkinsonism. Project 2 (Dr. Galvan), will explore the spontaneous and task-related activity of corticostriatal and corticospinal neurons in the primary motor cortex (M1) and the supplementary motor area (SMA) in normal and parkinsonian monkeys, using an opto-tagging approach to identify the projection targets of the recorded neurons. Project 3 (Dr. Smith) will examine morphological changes in the M1 and SMA microcircuitry and parkinsonism-associated changes in the connectome of cortical projection neurons in primates, a topic that is virtually unexplored and of high relevance to the interpretation of data in projects 1 and 2. The clinical ‘Catalyst’ project 4 is an examination of parkinsonism-related changes in cortical activity in response inhibition tasks, studied in electrocorticography and electroencephalography signals in patients with PD. The functional experiments will also study the effects of levodopa and deep brain stimulation treatments in these paradigms. All projects will be supported by an administrative core (Core A, Dr. Wichmann, PI; Dr. Smith, Associate Director, Ms Holbrook, administrator), and by a service core that provides anatomical services to projects 1 and 2, behavioral assessments to projects 2 and 3, and statistical services to all projects (Core B, Dr. Galvan). A clinical core (Core C) will support project 4 with recruitment and logistic services for the human studies. In addition to pursuing its research mission (aim 1), the Center will help young scientists to develop their career in PD research (aim 2), and will engage in extensive outreach efforts, aimed at communicating the Center’s (and Udall Center network) research findings to the public (aim 3), reaching all age groups and background levels. As part of the outreach agenda, the center plans to organize annual outreach events for patients and their caregivers. Generous internal support funds will help the Center to fund some of its education and outreach missions, as well as its pilot grant program, designed to expand PD research at Emory.