Dynamics of Striatal Microcircuits during Action Selection and Inhibition

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

Tourette Syndrome is believed to arise from malfunctioning of neural circuits in the basal ganglia. However the nature of this malfunction is still unclear. In an intriguing recent TSA supported study, Vaccarino found that the brains of patients with TS have abnormally few parvalbumin containing neurons in the striatum—a region of the basal ganglia. Parvalbumin is a marker of a particular class of cells—the fast-spiking GABAergic interneurons. These cells represent only a few percent of the total neurons in the striatum, yet they have a powerful role in that they influence the timing of activity in the wider cell population. In normal behavior, fast-spiking interneurons may assist the process of correctly selecting one action by providing a broad inhibition of unwanted movements. We have found that the activity of individual fastspiking neurons in freely-moving animals can be monitored by using super-fine electrodes placed in the striatum. With TSA funding, we will examine, on a millisecond-by-millisecond timescale, how different classes of neurons in the striatum interact with one another as animals select one of a range of actions, and inhibit others that are incorrect or untimely. Our aim is to reveal how microcircuitry within the striatum normally operates, and therefore how a deficit in fast-spiking interneurons (as seen in TS) could produce malfunction. Greater understanding of these processes may open the door to the development of novel, more selective therapeutic approaches to TS with fewer potential side-effects. Joshua D. Berke, Ph.D. University of Michigan, Ann Arbor, Michigan Award: $75,000 This study is funded by a generous donation by Sol Barer, Ph.D. Tourette Association of America Inc.- Research Grant Award 2006-2007