Circadian rhythms are generated by the master pacemaker suprachiasmatic nucleus (SCN) in concert with local clocks throughout the body. Although many brain regions exhibit cycling clock gene expression, the identity of a discrete extra-SCN brain oscillator that produces rhythmic behavior has remained elusive. Here, we show that an extra-SCN oscillator in the lateral amygdala (LA) is defined by expression of the clock-output molecule mWAKE/ANKFN1. mWAKE is enriched in the anterior/dorsal LA (adLA), and, strikingly, selective disruption of clock function or excitatory signaling in adLAmWAKE neurons abolishes Period2 (PER2) rhythms throughout the LA. mWAKE levels rise at night and promote rhythmic excitability of adLAmWAKE neurons by upregulating Ca2+-activated K+ channel activity specifically at night. adLAmWAKE neurons coordinate rhythmic sensory perception and anxiety in a clock-dependent and WAKE-dependent manner. Together, these data reveal the cellular identity of an extra-SCN brain oscillator and suggest a multi-level hierarchical system organizing molecular and behavioral rhythms.

中文翻译：

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杏仁核振荡器协调细胞和行为节律


昼夜节律由主起搏器视交叉上核 （SCN） 与全身的局部时钟产生。尽管许多大脑区域表现出循环时钟基因表达，但产生节律行为的离散 SCN 外脑振荡器的身份仍然难以捉摸。在这里，我们表明外侧杏仁核 （LA） 中的 extra-SCN 振荡器是由时钟输出分子 mWAKE/ANKFN1 的表达定义的。mWAKE 在前/背侧 LA （adLA） 中富集，引人注目的是，adLAmWAKE 神经元中时钟功能的选择性破坏或兴奋性信号传导消除了整个 LA 的第 2 期 （PER2） 节律。mWAKE 水平在夜间升高，并通过上调 Ca2+ 激活的 K+ 通道活性来促进 adLAmWAKE 神经元的节律性兴奋性，特别是在夜间。adLAmWAKE 神经元以时钟依赖性和 WAKE 依赖的方式协调有节奏的感觉知觉和焦虑。总之，这些数据揭示了 SCN 外脑振荡器的细胞身份，并表明了一个组织分子和行为节律的多级分层系统。