Effects of arousal on the cicadian clock

大脑如何追踪时间的流逝？ 行为神经科学家认为，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律和外部昼夜周期之间的同步。 了解这种生物钟的功能已成为我的主要研究兴趣。 生物钟位于视交叉上核（SCN）。 这种异质结构接收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似乎还通过多突触通路调节许多参与睡眠和觉醒的重要区域。 虽然生物钟在调节觉醒中的作用已经得到了很好的研究，但觉醒对生物钟的影响还不太清楚。 我之前已经证明，睡眠期间的强制唤醒可以重置生物钟。 此外，我的学生和我已经证明，这种唤醒抑制SCN细胞中的基因表达和生化途径。 唤醒影响生物钟的途径仍然未知。 本研究的目的是研究参与觉醒的各种脑区和神经递质（基底前脑和中脑脑桥被盖的乙酰胆碱;蓝斑的去甲肾上腺素;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。

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.