Cellular analysis of mammalian circadian rhythms

哺乳动物昼夜节律的细胞分析

• 批准号: 170040-2009
• 负责人: Ralph, Martin
• 金额: $ 1.82万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=452191
• 关键词: Cellular; analysis; mammalian; circadian; rhythms

The primary focus of work in this laboratory is on how daily rhythms of behavior and physiology are generated. This includes research into the biology of the central clock in the hypothalamus, the suprachiasmatic nucleus, as well as how a hierarchy of clocks throughout the body are controlled either by the central clock or directly by sensory input. The proposed research therefore follows two interrelated approaches. The first is aimed at an understanding of how the central clock produces circadian rhythms. When we switch on a gene (casein kinase-1-epsilon) within this clock in a mouse, the period of the animal's behavioral rhythm shortens. We will now produce mice where the gene is switched on only in specific cells, to see how these cells are involved in rhythm generation. The second approach is aimed at understanding how animals adjust their daily rhythms by learning the time of day that significant events occur. This will be accomplished by teaching animals to expect appetitive or aversive conditions at defined times of day, then examining how and where the cellular activity responsible for the time of day memory occurs in the brain. Finally, we will ask how the central clock is able to synchronize the time learning system in the absence of significant event. The work will contribute to our understanding of how multiple timing mechanisms in the body are coordinated. Time of day conditioning is thought to underlie the rhythms of craving seen in addiction, and internal disorganization of the many clocks throughout the body has been shown to lead to physical and mental issues such as cardiovascular disease and depressive disorders, as well as cognitive impairment.

该实验室的主要工作重点是研究日常行为和生理节律是如何产生的。这包括研究下丘脑中央时钟的生物学，视交叉上核，以及整个身体的时钟层次如何由中央时钟或直接由感官输入控制。因此，拟议的研究遵循两个相互关联的方法。第一个目的是了解中央时钟如何产生昼夜节律。当我们在小鼠的这个时钟中启动一个基因（酪蛋白激酶-1-β）时，动物的行为节律周期就会缩短。我们现在将生产只在特定细胞中开启基因的小鼠，以观察这些细胞如何参与节律的产生。第二种方法旨在了解动物如何通过学习一天中发生重大事件的时间来调整它们的日常节奏。这将通过教导动物在一天中的特定时间期待食欲或厌恶的条件来实现，然后检查负责一天中时间记忆的细胞活动在大脑中是如何以及在哪里发生的。最后，我们将询问在没有重大事件的情况下，中央时钟如何能够同步时间学习系统。 这项工作将有助于我们了解体内多种计时机制是如何协调的。一天中的时间调节被认为是成瘾中出现的渴望节奏的基础，而全身许多生物钟的内部紊乱已被证明会导致身体和精神问题，如心血管疾病和抑郁症，以及认知障碍。