Role of GSK-3 in Drosophila Behavioral Plasticity

GSK-3 在果蝇行为可塑性中的作用

• 批准号: 6936810
• 负责人: IAN F KING
• 金额: $ 4.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936810
• 关键词: Drosophilidae; arthropod genetics; behavioral /social science research tag; behavioral genetics; behavioral habituation /sensitization; circadian rhythms; ethology; neural plasticity; odors; postdoctoral investigator; serine threonine protein kinase; startle reaction

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.

描述（由申请人提供）： 习惯化是神经可塑性的一种形式，其中生物体对重复刺激的反应减弱。当果蝇暴露在乙醇或乙酸乙酯等气味物中时，它们会受到惊吓，表现出短暂的过度活跃。然而，当苍蝇反复暴露于气味剂时，惊吓反应会减少。我们已经使用这种乙醇惊吓习惯行为作为遗传筛选的基础，该筛选已经确定了基因Shaggy（sgg）中的突变，该突变会损害习惯行为。SGG是哺乳动物信号蛋白糖原合成酶激酶3 β（GSK-3 β）的果蝇同源物。GSK-3 β是锂的目标，锂是情感障碍的主要治疗方法，可能在某些精神疾病中发挥重要作用。我们将研究sgg在习惯化行为中的作用。我们将确定SGG是否通过发育过程或成人神经生理学影响习惯化，我们将开始定义果蝇大脑中需要SGG活动以实现正常习惯化的区域。Sgg也参与昼夜节律调节，我们将定义昼夜节律周期对习惯化的影响。了解Sgg在基本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。