Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.

中文翻译：

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脉络丛是重要的生物钟组件。

哺乳动物昼夜节律钟具有下丘脑上视交叉上核（SCN）支配的组织结构。大脑本身包含多个基因座，这些基因座维持自主的昼夜节律，但尚不清楚非SCN时钟对这种等级的贡献。我们检查了各种脑基因座中时钟基因表达的昼夜节律振荡，发现与SCN相比，在小鼠中，脉络丛（CP）出现了健壮的，更高的振幅，相对更快的振荡。我们的计算分析和建模表明，CP通过间隙连接实现了“扭曲”生物钟振荡器的同步，从而获得了这些特性。使用体外组织共培养模型和Bmal1基因的体内靶向缺失来沉默CP昼夜节律，