Research suggests that at least some of the symptoms of Tourette Syndrome (TS) may result from a dysfunction within the basal ganglia and other related regions of the brain. Alterations in structure or function have been demonstrated in some individuals in a part of the basal ganglia known as the caudate/putamen, or the striatum. Although the basal ganglia, including the striatum, have been the subject of intense investigation for the past three decades (driven largely by a need to understand the neural basis of diseases of these nuclei), the means by which these brain circuits produce both normal and abnormal motor behavior is still a mystery. We do know that the striatum somehow interacts with the cortex to provide for the organization, control and execution of movements. The ability of these brain circuits to correctly use envi¬ronmental cues, such as sensory stimuli, to aid in movement organi¬zation and control is a crucial component of their functioning, and may be part of the problem in TS. However, because the striatum is embedded within ascending and descending motor circuits, with no direct sensory or motor connections to the periphery, it has been difficult to determine its exact contribution to motor control. Today there is widespread appreciation that new insights about the basal ganglia and its associated cortical input will arise from an understanding of its “network properties,” i.e., the interactions among groups of neurons in these brain regions. In other words, it is important to understand how our neurons work together to produce motor behavior. Researchers have known for a long time that the contribution of any single one of our millions of neurons is very small, and rather it is the way in which our interconnected nets of neurons function together that determines brain function. However, until now, the means to investigate neuronal network function have been limited. New, sophisticated imaging techniques in humans have spurred this exciting exploration. Also, new means of recording the electrical activity of many individual neurons simultaneously in experimental animals are helping us better understand network properties of neurons. Our focus will be to investigate the network properties of the striatum and cortical regions that project to the striatum during sensory-motor tasks in which performance by individuals with TS is known to be impaired. These studies will use new experimental techniques that permit simultaneous recording of as many as fifty neurons at a time in rats performing stimulus-cued movement tasks that mirror the type of neuropsychological tests that are difficult for some people with TS. Studying activity of neuronal populations will provide insights into the nature of how coordinated neural activity is disrupted in disorders of the corticostriatal system. Patricia H. Janak, Ph.D. Bowman Gray School of Medicine Winston-Salem, NC Award: $39,600 Tourette Association of America Inc. – Research Grant Award 1997