Network Dynamics Mediate Circadian Clock Plasticity.
Network Dynamics Mediate Circadian Clock Plasticity.
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网络动力学介导昼夜节律的塑性。
DOI：
10.1016/j.neuron.2016.12.022
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发表时间：
2017-01-18
期刊：
影响因子：
16.2
通讯作者：
Brown SA
中科院分区：
文献类型：
--
作者：
Azzi A;Evans JA;Leise T;Myung J;Takumi T;Davidson AJ;Brown SA
生物钟控制着哺乳动物行为的大部分方面。虽然它的特性部分是由遗传决定的，但改变的光暗环境可以通过需要从头DNA甲基化的机制改变昼夜节律周期长度。我们在这里表明，这种机制是介导的，而不是通过细胞自主时钟特性，而是通过改变网络内的视交叉上核（SCN），昼夜节律的“主时钟”，这是DNA甲基化的区域特异性的方式。DNA甲基化对于在SCN神经元之间暂时重组昼夜节律相位是必要的，这反过来又改变了整个网络的周期长度。通过抑制神经元放电或通过物理切割来中断神经通信抑制SCN重组和周期变化。数学模型表明，实验证实，这种SCN重组依赖于GABA能信号。因此，我们的研究结果表明，基本的生物钟特性是由SCN神经元之间的动态相互作用，与环境驱动的网络功能的神经适应。
A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian “master clock”, which is DNA-methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole. Interruption of neural communication by inhibiting neuronal firing or by physical cutting suppresses both SCN reorganization and period changes. Mathematical modeling suggests, and experiments confirm, that this SCN reorganization depends upon GABAergic signaling. Our results therefore show that basic circadian clock properties are governed by dynamic interactions among SCN neurons, with neuroadaptations in network function driven by the environment.