Melanopsin-dependent photo-perturbation reveals desynchronization underlying the singularity of mammalian circadian clocks
Melanopsin-dependent photo-perturbation reveals desynchronization underlying the singularity of mammalian circadian clocks
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DOI：
10.1038/ncb1653
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发表时间：
2007-11-01
影响因子：
21.3
通讯作者：
Ueda, Hiroki R.
中科院分区：
文献类型：
--
作者：
Ukai, Hideki;Kobayashi, Tetsuya J.;Ueda, Hiroki R.
生物钟的奇点行为(1，2)--在受到诸如强光脉冲的刺激后失去强健的昼夜节律--是时钟的基本但神秘的特性之一。为了定量扰动和准确测量细胞时钟(3，4)的动力学，我们通过外源引入光感受器黑素(5-8)并持续监测光扰动对细胞时钟状态的影响，在哺乳动物细胞内合成了光响应性。在这里，我们报告了一个关键的光脉冲驱动细胞时钟进入奇点行为。我们的理论分析一致地预测，随后的单细胞水平观察直接证明了单个细胞时钟的去同步是奇点行为的基础。我们的理论框架还解释了为什么在各种生物体中实验观察到奇点行为，它表明去同步是昼夜节律时钟可观察到的奇点的一种合理的机制。重要的是，这些在体外和在电子计算机上的发现进一步得到了体内观察的支持，即去同步化是关键光脉冲导致大鼠视交叉上核多细胞水平幅度降低的基础。
Singularity behaviour in circadian clocks(1,2) - the loss of robust circadian rhythms following exposure to a stimulus such as a pulse of bright light - is one of the fundamental but mysterious properties of clocks. To quantitatively perturb and accurately measure the dynamics of cellular clocks(3,4), we synthetically produced photo-responsiveness within mammalian cells by exogenously introducing the photoreceptor melanopsin(5-8) and continuously monitoring the effect of photo-perturbation on the state of cellular clocks. Here we report that a critical light pulse drives cellular clocks into singularity behaviour. Our theoretical analysis consistently predicts and subsequent single-cell level observation directly proves that desynchronization of individual cellular clocks underlies singularity behaviour. Our theoretical framework also explains why singularity behaviours have been experimentally observed in various organisms, and it suggests that desynchronization is a plausible mechanism for the observable singularity of circadian clocks. Importantly, these in vitro and in silico findings are further supported by in vivo observations that desynchronization underlies the multicell-level amplitude decrease in the rat suprachiasmatic nucleus induced by critical light pulses.