The most reliable treatment for Tourette Syndrome (TS) remains the use of drugs which block the activity of the neurotransmitter dopamine (DA). This suggests that DA systems in the brain are hyperactive in TS patients. The question then becomes: What brain regions might be responsible for exciting the activity of DA cells in the central nervous system? Previous research from our laboratory, and others, has demonstrated that the pedunculopontine tegmental nucleus (PPN) is one of only a few brain regions which exert an excitatory influence on DA cells. We propose to use electrophysiological techniques to record the activity of single DA cells in the rat brain while either stimulating the PPN or after having removed the PPN. We will also assess the responsiveness of DA cells to a variety of experimental drugs following experimental manipulation of PPN activity. In subsequent experiments, microiontophoretic techniques will be used to study the role of glutamate and acetylcholine as potential neurotransmitters utilized by PPN projections to DA cells. This technique allows the administration of drugs directly onto single cells while the activity of that same cell is recorded. These data will then serve as a guide for chronic drug administration experiments, which will both provide basic data on the effects of chronic administration of glutamate antagonists on the activity of DA cells and pharmacologically mimic the effects of removing the PPN. These experiments should provide us with a better understanding of the excitatory regulation of DA cells. Since DA overactivity is implicated in many cases of TS, PPN-induced excitation of DA cells may be involved in the development of this disorder. Identifying the neurotransmitter involved may help lead us to new and better treatments for TS. Mark D. Kelland, Ph.D., Center for Cell Biology Sinai Hospital, Detroit, MI Award $17,168 Tourette Association of America Inc. – Research Grant Award 1993