Regulation of Intrinsic Plasticity in Neural Circuits

描述（由申请人提供）：学习和记忆的能力是一项重要的生存技能，无论你是人类还是苍蝇。这一建议将利用果蝇的行为和遗传丰富性来定义和理解连接睡眠和记忆的神经元回路。人类一生中大约有三分之一的时间在睡觉。令人惊讶的是，关于我们和其他动物为什么要睡觉，人们并没有达成共识，只是一致认为，没有睡眠，我们的大脑就不能发挥最佳功能。一个反复出现的发现，从人类、哺乳动物模型系统和果蝇那里得到的令人信服的数据是，睡眠是有效记忆形成所必需的。我们将使用改变神经元兴奋性的细胞特异性操作来研究生物钟在睡眠（特定目标#1）和记忆形成（特定目标#2）中的作用。我们将识别和描述产生睡眠的生物钟下游细胞的活动（具体目标#3）。在西方社会，睡眠不足是一个日益严重的人类健康问题。对果蝇睡眠和记忆之间联系的研究将有助于我们了解睡眠如何影响人类的学习能力。

DESCRIPTION (provided by applicant): The ability to learn and remember is a critical survival skill whether you are a human or a fly. This proposal will exploit the behavioral and genetic richness of Drosophila to define and understand neuronal circuits that link sleep and memory. Humans spend roughly one third of their lives asleep. Amazingly, there is no consensus on why we and other animals sleep, only agreement that without sleep our brains do not function optimally. One recurring finding, with convincing data from humans, mammalian model systems, and Drosophila is that sleep is required for effective memory formation. We will investigate the role of the circadian clock in both sleep (Specific Aim #1) and memory formation (Specific Aim #2) using cell specific manipulations that alter neuronal excitability. We will identify and characterize the activity of cells that are downstream of the clock that generate sleep (Specific Aim #3). PUBLIC HEALTH RELEVANCE Lack of sleep is an increasingly serious human health problem in western society. Studies of the linkage between sleep and memory in Drosophila will provide insight into how sleep affects learning in humans.