Dynamics od Striatal Microcircuits during Action Selection and Inhibition

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Michigan
Investigators Name
Berke, Joshua, PhD

TS is believed to arise from malfunctioning of neural circuits involving the basal ganglia, yet the nature of this malfunction has remained unclear. An intriguing recent TSA-supported study found that in one part of the basal ganglia, the striatum, TS patients have abnormally few parvalbumin containing neurons. Parvalbumin is a marker of a particular class of cells, the fastspiking GABAergic interneurons. While these cells represent only a small number of the total neurons in the striatum, they exert a powerful influence on the activity in the wider cell population. In normal behavior, by providing a broad inhibition of unwanted movements, fastspiking interneurons may assist the process of correctly selecting one action. We have found that by using advanced electrophysiological techniques we can monitor the activity of individual fast-spiking neurons in freely-moving animals. With TSA funding, we have begun to examine, on a millisecond-by-millisecond timescale, how different classes of neurons in the striatum interact with one another as animals select actions and inhibit others that are incorrect or untimely. During the first year of TSA support we began to amass a data set that challenges existing conceptions of the contribution of fast-spiking striatal interneurons to behavior. In the second year we will complete this study and extend our investigation by looking at the activity of these cells during learning. We will also examine the effects of neuroleptic drugs (currently used to treat TS) on interneuron activity. Our ultimate aim is to reveal how micro-circuitry within the striatum normally operates. In this way we can deduce how a deficit in fast-spiking interneurons (as seen in TS) would produce malfunction. Greater understanding of these processes may open the door to novel, more selective therapeutic approaches to TS with potentially fewer side-effects. Joshua D. Berke, Ph.D. University of Michigan Ann Arbor, MI Award: $75,000 (Year 2) Tourette Association of America Inc. – Research Grant Award 2007-2008