Division of Neurobiology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Science. 2019 Jan 11;363(6423):187-192. doi: 10.1126/science.aat4104.
Circadian (~24-hour) rhythms depend on intracellular transcription-translation negative feedback loops (TTFLs). How these self-sustained cellular clocks achieve multicellular integration and thereby direct daily rhythms of behavior in animals is largely obscure. The suprachiasmatic nucleus (SCN) is the fulcrum of this pathway from gene to cell to circuit to behavior in mammals. We describe cell type-specific, functionally distinct TTFLs in neurons and astrocytes of the SCN and show that, in the absence of other cellular clocks, the cell-autonomous astrocytic TTFL alone can drive molecular oscillations in the SCN and circadian behavior in mice. Astrocytic clocks achieve this by reinstating clock gene expression and circadian function of SCN neurons via glutamatergic signals. Our results demonstrate that astrocytes can autonomously initiate and sustain complex mammalian behavior.
昼夜节律（约 24 小时）依赖于细胞内转录-翻译负反馈环（TTFL）。这些自我维持的细胞时钟如何实现细胞间的整合，从而指导动物的日常行为节律，在很大程度上还不清楚。视交叉上核（SCN）是哺乳动物从基因到细胞到回路再到行为的这个途径的枢轴。我们描述了 SCN 神经元和星形胶质细胞中特定于细胞类型的、功能不同的 TTFL，并表明，在没有其他细胞时钟的情况下，细胞自主的星形胶质细胞 TTFL 本身就可以驱动 SCN 中的分子振荡和小鼠的昼夜节律行为。星形胶质细胞通过谷氨酸能信号来恢复 SCN 神经元的时钟基因表达和昼夜节律功能来实现这一点。我们的结果表明，星形胶质细胞可以自主启动和维持复杂的哺乳动物行为。
