Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms
Regulating the Suprachiasmatic Nucleus (SCN) Circadian Clockwork: Interplay between Cell-Autonomous and Circuit-Level Mechanisms
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DOI：
10.1101/cshperspect.a027706
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发表时间：
2017-01-01
影响因子：
7.2
通讯作者：
Hastings, Michael H.
中科院分区：
文献类型：
--
作者：
Herzog, Erik D.;Hermanstyne, Tracey;Hastings, Michael H.
视交叉上核（SCN）是大脑的主要生物钟，指导着行为和生理的日常周期。SCN神经元包含一种基于细胞自主性转录的生物钟机制，而反过来，回路层面的相互作用将约20,000个SCN神经元同步为一个强大且连贯的日常计时器。同步需要神经肽信号传导，这由分子生物钟机制和节律性电活动之间的相互依赖所调节，而节律性电活动又依赖于白天的钠离子驱动和夜间的钾离子拖拽。近期利用交叉遗传学的研究已经开始确定SCN中特定神经元群体的起搏作用。它们支持这样一种观点，即计时涉及非线性和分级计算，这些计算通过SCN回路内关键神经元群体之间的相互作用产生并整合计时信息。该领域现在已准备好阐明这些计算、其潜在的细胞机制，以及SCN生物钟如何与大脑各处的从属生物钟相互作用以确定睡眠 - 觉醒周期的时间和效率，以及这种连贯性的扰动如何导致神经和精神疾病。
The suprachiasmatic nucleus (SCN) is the principal circadian clock of the brain, directing daily cycles of behavior and physiology. SCN neurons contain a cell-autonomous transcription-based clockwork but, in turn, circuit-level interactions synchronize the 20,000 or so SCN neurons into a robust and coherent daily timer. Synchronization requires neuropeptide signaling, regulated by a reciprocal interdependence between the molecular clockwork and rhythmic electrical activity, which in turn depends on a daytime Na+ drive and nighttime K+ drag. Recent studies exploiting intersectional genetics have started to identify the pacemaking roles of particular neuronal groups in the SCN. They support the idea that timekeeping involves nonlinear and hierarchical computations that create and incorporate timing information through the interactions between key groups of neurons within the SCN circuit. The field is now poised to elucidate these computations, their underlying cellular mechanisms, and how the SCN clock interacts with subordinate circadian clocks across the brain to determine the timing and efficiency of the sleep-wake cycle, and how perturbations of this coherence contribute to neurological and psychiatric illness.