Perturbations in Early Striatal Development as a Basis for Later Neurological Dysfunction

Grant Type
Basic
Grant Year
1989
Institution Location
NY
Institution Organization Name
NYS Dept. of Health
Investigators Name
Snyder-Keller, Abigail, PhD

The neuropathology underlying Tourette Syndrome appears to involve the basal ganglia, although its precise nature is not clear. The striatum is a key integrative structure of the basal ganglia, and anatomical studies have revealed an intricate compartmentalized organization to that structure. Because this organization is likely to be the basis of proper processing of information through the striatum, defects in its development may have profound neurological consequences. Little is known about how the various cell types found there become organized with respect to each other. In order to determine the key features of the development of the striatum, we will alter the development in two different ways, and determine how these manipulations affect the distribution of the major cell types, identified by labelling with antibodies to the various substances present. The first experiment will be to assess the effects of destroying the dopaminergic projections to the striatum early in development, because dopamine-containing cells grow very early into the striatum, and the use of antidopaminergic drugs in Tourette Syndrome indicates that some imbalance involving dopamine has occurred in the brain. The second experiment will involve the destruction of a subpopulation of cells that are the first to be born in the striatum. These cells are known to associate with each other in clusters, and their removal may prevent the proper organization of cells generated later. In both cases we will determine whether the distribution of the striatal cells is altered with respect to their organization in normal brains, and to the distribution of dopamine projections. It is expected that by increasing our knowledge of the critical processes in the development of the striatum, these studies will provide insights as to how a genetic defect can alter the organization of basal ganglia structures implicated in Tourette Syndrome so as to result in abnormal functioning. Abigail M. Snyder-Keller, Ph.D., Laboratory of Neurotoxicology and Nervous System Disorders NYS Dept. of Health, Wadsworth Center for Laboratories and Research, Albany, NY Award: $22,280 Tourette Association of America Inc. – Research Grant Award 1989