Effects of arousal on the cicadian clock

觉醒对蝉钟的影响

• 批准号: 311874-2010
• 负责人: Antle, Michael
• 金额: $ 5.17万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526287
• 关键词: Effects; arousal; cicadian; clock

How does the brain track the passage of time? Behavioural neuroscientists believe that a circadian clock located in the hypothalamus coordinates the temporal patterns in physiology and behaviour, and maintains synchrony between these endogenous rhythms and the external day-night cycle. Understanding how this circadian clock functions has become my main research interest. The circadian clock is located in the suprachiasmatic nucleus (SCN). This heterogeneous structure receives input from the eye and various other brain regions, and projects directly to other hypothalamic and thalamic areas. Further more, the SCN appears to regulate many important areas involved in sleep and wake through multisynaptic pathways. While the role that the circadian clock plays in regulating arousal is well studied, the effects of arousal on the circadian clock are less well understood. I have previously shown that enforced arousal during the sleep period can reset the circadian clock. Furthermore, my students and I have shown that such arousal inhibits gene expression and biochemical pathways in SCN cells. The pathway by which arousal affects the clock remains unknown. The goal of this proposal is to examine how the various brain areas and neurotransmitters known to participate in arousal (acetylcholine from the basal forebrain and mesopontine tegmentum; norepinephrine from the locus coeruleus; serotonin from the raphe) affect circadian responses at the molecular, tissue and behavioural levels. The present proposal has the short-term goal of understanding how arousal affects the circadian clock.

大脑如何跟踪时间的流逝？行为神经学家认为，位于下丘脑的生物钟协调生理和行为的时间模式，并保持这些内源性节奏和外部昼夜周期之间的同步。了解这种生物钟是如何工作的，已经成为我的主要研究兴趣。生物钟位于视交叉上核(SCN)。这种异质结构接受来自眼睛和其他大脑区域的输入，并直接投射到其他下丘脑和丘脑区域。此外，SCN似乎通过多突触通路调节许多涉及睡眠和觉醒的重要区域。虽然人们很好地研究了生物钟在调节唤醒中所起的作用，但唤醒对生物钟的影响却知之甚少。我之前已经证明，在睡眠期间强制唤醒可以重置生物钟。此外，我和我的学生已经证明，这种觉醒抑制了SCN细胞中的基因表达和生化途径。唤醒影响生物钟的途径尚不清楚。这项提议的目的是研究已知的参与觉醒的不同脑区和神经递质(来自基底前脑和桥中脑被盖的乙酰胆碱；来自蓝斑的去甲肾上腺素；来自中缝的5-羟色胺)如何在分子、组织和行为水平上影响昼夜节律反应。目前的建议有一个短期目标，即了解唤醒如何影响生物钟。