Tourette Syndrome (TS) is associated with distinct stereotypical movements and behaviors. Malfunction of the basal ganglia and the prefrontal cortex (PFC) has been implicated in TS, but the nature of involvement of each region is not clear. A better understanding of the factors that govern the functional communication between basal ganglia and PFC would help us to develop more efficient strategies to treat both tics and the behavioral symptoms of TS. In this study we will determine how neuronal activity in the PFC and striatum correlates with expression and suppression of tic-like stereotypy in pharmacological animal models. These experiments are designed to allow us to monitor the activity of a group of neurons. Stereotypy behavior will first be induced by either blocking NMDA glutamate receptors or activating dopamine receptors, and then the behavior will be suppressed by a standard anti-tic drug. We hypothesize that miscommunication between the PFC and striatum will induce disinhibited behaviors. The ongoing studies will determine how the activity of groups of neurons in the PFC and striatum are integrated at a large-scale during the expression of stereotypy. Based on modulation of a class of glutamate receptors we will also explore a novel pharmacological strategy which may suppress repetitive movements through influencing corticostriatal signal to noise ratio. These experiments will help us understand the mechanisms that contribute to corticostriatal dysregulation at both single cell and network levels. Houman Homayoun, M.D. University of Pittsburgh, Pittsburgh, Pennsylvania Award: $35,000 (2nd Year) Tourette Association of America Inc. – Research Grant Award 2006-2007