Genetic dissection of circadian pacemaker function in the suprachiasmatic nucleus

视交叉上核昼夜节律起搏器功能的基因剖析

• 批准号: 372813-2010
• 负责人: Storch, KaiFlorian
• 金额: $ 2.33万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=550186
• 关键词: Genetic; dissection; circadian; pacemaker; function

Circadian clocks drive rhythms in physiology and behavior with a period of about 24 hours. In mammals the master circadian oscillator is located in the suprachiasmatic nucleus (SCN), a paired structure at the base of the brain. Each hemisphere consists only of about 20,000 neurons in mice or 45,000 in humans that oscillate in synchrony in order to transmit a coherent timing signal across the body axis permitting an optimal physiological and behavioral response to the environmental changes dictated by the solar day. It is suggested that the SCN is functionally divided into subcompartments, however, in vivo evidence in support of this view is still largely lacking. Using a novel genetic strategy, we plan to systematically eliminate or restore rhythm generating from distinct subdivisions of the mouse SCN and then test for functional consequences in vivo. These experiments might not only shed light on the fundamental question regarding the existence of functional SCN subdivisions, but may also reveal how rhythmic synchrony is maintained among SCN neurons. Because SCN neurons innervate various brain areas, it is likely that the proposed research will yield a high resolution, functional map of SCN pacemaker targets in the brain. Ultimately, these studies are likely to provide critical insights into the poorly understood mechanisms underlying the temporal organization of mammalian sleep, feeding, and locomotor behavior.

生物钟以大约 24 小时为周期驱动生理和行为节律。在哺乳动物中，主要的昼夜节律振荡器位于视交叉上核（SCN），这是大脑底部的成对结构。每个半球仅由小鼠的约 20,000 个神经元或人类的 45,000 个神经元组成，这些神经元同步振荡，以便在整个身体轴上传输连贯的定时信号，从而对太阳日所决定的环境变化做出最佳的生理和行为反应。有人认为视交叉上核在功能上分为多个子区室，然而，仍然缺乏支持这一观点的体内证据。使用一种新的遗传策略，我们计划系统地消除或恢复小鼠 SCN 不同细分产生的节律，然后测试体内的功能后果。这些实验不仅可能揭示有关功能性 SCN 细分存在的基本问题，而且还可能揭示 SCN 神经元之间如何维持节律同步。由于 SCN 神经元支配不同的大脑区域，因此拟议的研究很可能会产生大脑中 SCN 起搏器目标的高分辨率功能图。最终，这些研究可能为人们对哺乳动物睡眠、进食和运动行为的时间组织机制知之甚少提供重要见解。