Neurophysiological Basis of Response Inhibition in Corticostriatal Systems

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Laubach, Mark, PhD

The alpha (2A)-adrenergic receptor agonist, guanfacine, is known to improve some of the symptoms of Tourette Syndrome. However, the effects of guanfacine on brain structures implicated in TS, such as the frontal cortex and basal ganglia, are not well understood. In this project, we will examine how guanfacine alters neuronal activity in these brain structures during the performance of a simple motor task. For this task, the rats must learn to maintain a behavioral response over an unpredictable interval of time. They commit errors when they “jump the gun” by responding prematurely. Psychologists often attribute this kind of behavior to a process of response inhibition that allows one to execute an appropriate motor response while inhibiting competing motor tendencies. This project has three components. First, we will study what happens to response inhibition when the frontal cortex is turned off, which is known to lead to an increase in premature responding. Second, we will study what happens when guanfacine is administered directly into the frontal cortex, the effects of which are entirely unknown. Third, we will record brain cell activity in the frontal cortex and basal ganglia during the normal performance of our task and also following infusions of guanfacine into the frontal cortex. These studies will reveal how guanfacine alters nerve cell activity in brain structures that are both critical for response inhibition and have been implicated in TS. We believe that this research will lead to a model system for evaluating the neurobiological basis of the effects of drugs that are used to treat TS and other tic disorders. Mark Laubach, Ph.D. Yale University School of Medicine, New Haven, CT Award: $67,351 Tourette Association of America Inc. – Research Grant Award 2004-2005