Our study is designed to test the idea that the motor disorder of Tourette Syndrome results from a disruption of brain mechanisms normally controlling sequences of movement. Sequences of movement are crucial to nearly all behavior. Many of our sequential movements are so effortless and natural to us that we might take for granted one important feature they share. Each sequence requires the coordination of many skilled behavioral elements. Each motor element must be initiated in the proper order at the proper time. With so many movements, it is not enough to know what to do: one must also know in what order and when to perform the movement. While some movements, such as walking, are obviously sequential, other more complex motor behaviors, such as speech, are also critically dependent on a sequential structure. In order for us to survive, the brain has evolved to control sequences of behavior. Our study focuses on the basal ganglia which we believe play a critical role in controlling sequences of behavior. We also believe that dopamine, one of the important neurotransmitter systems in the basal ganglia, plays an important role in controlling sequences. Neurotransmitters are chemicals released by nerve cells to increase or decrease the activity of other nerve cells. These relationships may explain why drugs that modulate dopamine are important in treating Tourette Syndrome symptoms. We will investigate two specific ideas. First, we will test the idea that the basal ganglia help to control sequences of movements by regulating sensory information. The goal is to examine brain mechanisms participating in the process of deciding “what to do, in what order and when to do it.” Our idea is that basal ganglia will act as a gateway to control the flow of sensory information used to guide sequences of behavior. We will test this theory by recording the activity of individual brain cells (neurons) in rodents during sequential grooming behavior. (Rodent grooming provides an ideal model for testing sequential movements as it is instinctive, rigid in form (stereotyped) and depends on the basal ganglia.) If the basal ganglia are damaged in rats, sequential grooming is disturbed. Therefore we will compare brain activity in normal animals with animals that have sensory input reduced. Secondly, we will test whether drugs affecting dopamine alter activity in basal ganglia neurons related to sequences of movement in rodents during grooming. We will record activity from individual neurons while applying drugs that enhance or block dopamine. We anticipate that drugs enhancing dopamine will increase natural grooming sequences along with corresponding activity in the neuronal circuits of the basal ganglia. We theorize that dopamine blockers should do the reverse–that is decrease the activity. We hope that by evaluating these reactions we can make a meaningful contribution to the understanding of the neuronal mechanisms of Tourette Syndrome as well as provide a model for future investigations and tests of therapeutic drugs. J. Wayne Aldridge, Ph.D. University of Michigan, Ann Arbor, MI Award $48,783 Tourette Association of America Inc. – Research Grant Award 1995