Udall Center-Emory University

 

 

Director: Thomas Wichmann, MD

Title: Udall Parkinson's Disease Research Center at Emory University

Website:http://www.udall.emory.edu/

 

Central Theme

Research at the Udall Center at Emory University is concerned with the pathophysiology of Parkinson’s disease, and the mechanisms by which antiparkinsonian treatments work, from a brain circuit perspective. Treatment optimization is only possible if the biology of the basal ganglia thalamocortical circuitry under normal and parkinsonian conditions and the effects of therapeutic interventions such as deep brain stimulation are better understood. A specific shortcoming of current pathophysiologic models of parkinsonism is that they tend to concentrate almost exclusively on the basal ganglia, while their impact on other brain network elements (thalamus and cortex) is much less understood. These parkinsonism-related changes ‘downstream’ from the basal ganglia are the focus of studies at the Emory Udall Center. The projects focus on anatomical and functional changes in synaptic transmission in thalamus and cortex, and the effects of basal ganglia interventions such as deep brain stimulation on these circuit elements in rodent and nonhuman primate models of Parkinson’s disease. The 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, to optimize existing neuromodulation strategies, and to develop new antiparkinsonian therapies.

 

Center Structure

The Emory Udall Center brings together researchers from several departments at Emory University with complementary strong expertise in systems-centered Parkinson’s disease research. The Center fosters a collaborative, efficient, and productive environment for such research, allowing easy sharing of information and resources. Additional important goals of the center are to facilitate communication and discussions between all investigators involved in Parkinson’s disease research at Emory University, and to educate young researchers and the general public about research in this field.

The Udall Center at Emory University consists of three tightly linked research projects and two cores.

Project 1: Synaptic integration of cortical and nigral input in parkinsonian mouse motor thalamus (Dieter Jaeger, PhD) utilizes 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: Corticothalamic and thalamocortical Interactions in parkinsonian monkeys (Thomas Wichmann, MD) explores thalamic and cortical abnormalities in parkinsonian monkeys, using selective optogenetic and other activation and inactivation approaches to study corticothalamic, pallidothalamic and thalamocortical information transfer.

Project 3: Structural pathology of the motor thalamo-cortico-thalamic system in Parkinson's disease (Yoland Smith, PhD) examines morphological changes in the thalamic and cortical microcircuitry in parkinsonian primates, based on exciting new findings of parkinsonism-related anatomical abnormalities of the interactions between thalamus and cortex,

The Center’s Administrative Core (Dr. Wichmann) coordinates the interactions between the different investigators and their laboratories, facilitates interactions with the overall Udall Center network, the NIH, as well as local and external advisors. The core also organizes local meetings, administers the Center’s pilot grant program, maintains the Center’s website, and organizes the Center’s education and outreach activities. The Anatomy and Behavior Core (Adriana Galvan, PhD) will provide immunohistochemistry and electron microscopy services to projects 1-3, standardized animal models and quantification of parkinsonism from materials in projects 2 and 3.

Research at the Emory Udall Center addresses several of the NINDS PD2014 research priorities, including

  • Basic Research Recommendation 3, Understand how different cell populations change in their coding properties, firing patterns, and neural circuit dynamics over time; how they relate to behavior and motor control; and how therapeutic interventions may affect such changes.
  • Basic Research Recommendation 9, Use a combination of sensor technologies … to develop a more precise understanding of the neural circuit dynamics in PD to enable the development of next-generation therapeutic devices

 

Publications from the Emory Udall Center
 

Resources Available

Researchers at the Emory Udall Parkinson’s Disease Center share electrophysiologic data and data analysis algorithms. In addition, the Center makes primate brain tissue samples available to researchers. Notably, these tissue samples are a highly limited and valuable resource; sharing will therefore be prioritized by committee, based on the research for which the tissue is requested.


Public Health Statement

One goal of research of Emory’s Udall Center is to develop a better understanding of how the loss of dopamine and other changes in the brain lead to the physical symptoms of Parkinson’s Disease, as well as how existing surgical and medical treatments for people with PD work through brain circuitry. While previous studies have largely focused on disease- or treatment-related changes on the activity of nerve cells in the basal ganglia, i.e., the brain areas that are immediately affected by dopamine loss in Parkinson’s disease, some of the Center’s studies will examine the downstream effects of these interventions, focusing on the thalamus and cerebral cortex. The thalamus is the anatomical bridge by which basal ganglia output is linked to the cerebral cortex. Abnormalities in the activity of the cerebral cortex directly affect movement, and may lead to the movement abnormalities in Parkinson’s disease. Another focus of Center research is to pursue exciting new discoveries of changes in the anatomical structure of connections between the thalamus and cortex, with studies aimed at understanding how these changes relate to Parkinson’s disease.  Knowledge gained from the coordinated efforts of Center researchers will help to develop new pharmacologic and surgical therapies to treat parkinsonian symptoms, and to optimize existing treatment approaches.