Role of GSK-3 in Drosophila Behavioral Plasticity

描述(由申请人提供)： 习惯化是一种神经可塑性，在这种情况下，有机体对重复刺激的反应会减弱。当果蝇接触到乙醇或乙酸乙酯等气味时，它们会受到惊吓，表现出短暂的多动。然而，当苍蝇反复接触这种气味时，惊吓反应会减少。我们已经使用这种酒精惊吓习服行为作为基因筛查的基础，该筛查已经确定了Shaggy(SGG)基因的突变，该突变会损害习服行为。SGG是哺乳动物信号蛋白糖原合成酶激酶3β(GSK-3β)在果蝇中的同系物。GSK-3beta是锂的靶点，锂是治疗情感障碍的主要药物，可能在一些精神疾病中发挥重要作用。我们将探讨SGG在习惯性行为中的作用。我们将确定SGG是否通过发育过程或成年神经生理学影响习服，我们将开始定义果蝇大脑中需要SGG活动才能正常习服的区域。SGG也参与昼夜节律调节，我们将定义昼夜节律对习惯化的影响。了解SGG在基础神经可塑性中的作用将有助于理解精神疾病中涉及的更复杂的过程。

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.