Role of GSK-3 in Drosophila Behavioral Plasticity

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DESCRIPTION (provided by applicant): Habituation is a form of neural plasticity in which an organism's response to a repeated stimulus attenuates. When Drosophila are exposed to an odorant such as ethanol or ethyl acetate they startle, showing a transient burst of hyperactivity. However, the startle response is reduced as flies are exposed to the odorant repeatedly. We have used this ethanol-startle habituation behavior as the basis for a genetic screen, which has identified a mutation in the gene Shaggy (sgg) that impairs habituation behavior. Sgg is the Drosophila homologue of the mammalian signaling protein glycogen synthase kinase 3beta (GSK-3beta). GSK-3beta is a target for Lithium, a major treatment for affective disorders, and might play an important part in some mental illnesses. We will investigate the role of sgg in habituation behavior. We will determine whether sgg affects habituation through developmental processes or adult neurophysiology and we will begin to define the regions of the Drosophila brain that require sgg activity for normal habituation. Sgg also participates in circadian regulation, and we will define the effects of the circadian cycle on habituation. Understanding Sgg's role in basic neuroplasticity will aid understanding of the more complex processes involved in mental illness.