Localization of Cell Type-Specific Striatal Dysfunction in Dyt1 Dystonia
Abstract
Dystonia, the third most common movement disorder after tremor and Parkinson’s disease, is characterized by involuntary muscle contractions that cause debilitating twisting movements and postures. Treatments for dystonia are inadequate because the abnormal brain signals that cause dystonic movements are unknown. Abnormal signaling within the striatum, a brain region involved in the control of movement, is observed in many types of dystonia. Specifically, acetylcholine and dopamine signaling within the striatum are abnormal. However, we do not understand the causes of these signaling defects or how these defects impact the neuronal interactions that form microcircuits within the striatum. The goal of this proposal is to develop a more complete understanding of the causes and consequences of abnormal striatal signaling and circuits with the ultimate goal of restoring striatal function. To accomplish this goal, the proposed experiments will determine if the striatal signaling problems are caused by abnormalities in acetylcholine signaling or dopamine signaling or both. The findings of this proposal will have a direct impact on the development of therapeutics by providing a framework to guide therapeutic strategies aimed at modifying microcircuit activity. Modification of circuit-level defects for the treatment of dystonia is a completely new way of thinking about therapeutics for dystonia.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010446
Entities
People
- Ellen Hess
Organizations
- Emory University
- United States Army