The Morris K. Udall Parkinson's Disease Center of Excellence for Parkinson's Disease Research at Emory University is a collaborative research program in which electrophysiologists and anatomists study the pathophysiology of parkinsonism, and examine and optimize the effects of existing treatments for Parkinson's disease. The Center draws upon the proven ability of the basal ganglia research community at Emory to conduct translational research. Other Udall Center assets are its close ties to the clinical movement disorders group at Emory, and the availability of primates for research at the Yerkes National Primate Research Center at Emory University. Emory is strongly committed to the Udall Center's research, and supports the Center by funding pilot grants, invited speakers, and portions of its education and outreach programs. The Center consists of three tightly linked projects and two cores. The planned research will shed light on the poorly understood parkinsonism-related activity changes in thalamus and cortex which, in turn, will help us to better understand the pathophysiology of parkinsonism, and to optimize existing neuromodulation strategies and to develop new ones. Project 1 (led by Dr. Jaeger) will utilize brain slice and in vivo recordings in rodents, as well as a neural computational approach to develop mechanistic models of thalamocortical dysfunction in parkinsonism. Project 2 (Dr. Wichmann), will continue the exploration of thalamic and cortical abnormalities in parkinsonian monkeys, using selective activation and inactivation approaches which are designed to study corticothalamic, pallidothalamic and thalamocortical information transfer. Project 3 (Dr. Smith) will examine morphological changes in the thalamic and cortical microcircuitry in parkinsonian primates, a topic that is virtually unexplored at this time and of high relevance to the interpretation of data in the other projects. All projects will be supported by an Administrative Core (Dr. Wichmann, PI; Dr. DeLong, Co-I, Dr. Smith, Co-I, Ms Holbrook, administrator), and by an Anatomy and Behavior Core (Dr. Galvan) which will provide immunohistochemistry and electron microscopy services to all of the center projects, and standardized MPTP treatment and quantification of parkinsonism to the primate experiments in Projects 2 and 3. In addition to pursuing its research mission (Aim 1), the Center will help junior scientists to develop their career in Parkinson's disease 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, ranging from K-12 children to retirees in assisted living facilities. As part of the outreach agenda, the center plans to organize annual symposia for patients and their caregivers. The center will be generously supported by the University. These 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 Parkinson's disease research at Emory University.

Public Health Relevance

There continues to be an urgent need for antiparkinsonian treatments that are more effective and have fewer side effects than those currently available. To address this need, the research of the proposed Center will focus on generating a more detailed understanding of the pathophysiology of Parkinson's disease, especially the poorly understood abnormalities in thalamocortical interactions in the parkinsonian state, and on using this knowledge to develop or optimize neuromodulation approaches to Parkinson's disease. Apart from conducting highly collaborative and innovative research on Parkinson's disease, the Center will also train junior investigators, and educate the public about Parkinson's disease research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
1P50NS098685-01
Application #
9196040
Study Section
Special Emphasis Panel (ZNS1-SRB-J (12))
Program Officer
Sieber, Beth-Anne
Project Start
2016-09-30
Project End
2021-07-31
Budget Start
2016-09-30
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
$1,414,199
Indirect Cost
$589,197
Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Galvan, Adriana; Caiola, Michael J; Albaugh, Daniel L (2018) Advances in optogenetic and chemogenetic methods to study brain circuits in non-human primates. J Neural Transm (Vienna) 125:547-563
Masilamoni, Gunasingh J; Smith, Yoland (2018) Metabotropic glutamate receptors: targets for neuroprotective therapies in Parkinson disease. Curr Opin Pharmacol 38:72-80
Bhattacharya, Subhrajit; Ma, Yuxian; Dunn, Amy R et al. (2018) NMDA receptor blockade ameliorates abnormalities of spike firing of subthalamic nucleus neurons in a parkinsonian nonhuman primate. J Neurosci Res 96:1324-1335
Masilamoni, Gunasingh J; Smith, Yoland (2018) Chronic MPTP administration regimen in monkeys: a model of dopaminergic and non-dopaminergic cell loss in Parkinson's disease. J Neural Transm (Vienna) 125:337-363
Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R (2018) Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research. J Neural Transm (Vienna) 125:419-430
Villalba, Rosa M; Smith, Yoland (2018) Loss and remodeling of striatal dendritic spines in Parkinson's disease: from homeostasis to maladaptive plasticity? J Neural Transm (Vienna) 125:431-447
Galvan, Adriana; Stauffer, William R; Acker, Leah et al. (2017) Nonhuman Primate Optogenetics: Recent Advances and Future Directions. J Neurosci 37:10894-10903
Masilamoni, Gunasingh Jeyaraj; Groover, Olivia; Smith, Yoland (2017) Reduced noradrenergic innervation of ventral midbrain dopaminergic cell groups and the subthalamic nucleus in MPTP-treated parkinsonian monkeys. Neurobiol Dis 100:9-18
Raper, Jessica; Morrison, Ryan D; Daniels, J Scott et al. (2017) Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics. ACS Chem Neurosci 8:1570-1576