Functional and Structural Properties of Distinct Subpopulations of Striatal Neurons: Relation to the Pathophysiology of TS

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Pittsburgh
Investigators Name
Nisenbaum, Eric, PhD

Several lines of evidence suggest that some of the motor symptoms of Tourette Syndrome (TS) may result, in part, from dysfunction within the caudate-putamen complex (striatum). In order to understand the involvement of the striatum in neurological disorders such as TS, it is imperative first to define the cellular constituents and their local interactions, as well as the manner in which these subpopulations of neurons are influenced by neurotransmitter input. To this end, we recently have shown that two functionally distinct subpopulations of striatal cells, Type I and Type II, can be identified based on their contrasting responses to stimulation of cortical afferents. These differences provided the first conclusive evidence that striatal neurons could be segregated on the basis of their functional properties. In addition, and of potential clinical relevance, the activity of these two subclasses of striatal cells is differentially related to sensorimotor behaviors. The aims of the proposed experiments are 1) to examine potential differences (or similarities) in the morphological characteristics of these subclasses of neurons, and their relation to the neurochemical compartmentalization of the striatum, 2) to investigate potential differences in the regulation of their excitability by intrinsic membrane properties, and intrastriatal GABAergic and extrastriatal dopaminergic (DA) circuits, and 3) to examine alterations in the activity of these neurons within the DA receptor hypersensitivity model of TS. Results from these studies will provide relevant information concerning the critical variables (e.g., membrane properties, circuitry) which regulate the activity of striatal neurons, and possible insights into how such activity ultimately influences motor function. Eric S. Nisenbaum, Ph.D. University of Pittsburgh Pittsburgh, PA Award $20,000 – Fellowship (2nd yr.) Tourette Association of America Inc. – Research Grant Award 1991