Laboratory of Genetics, The Rockefeller University, New York, New York 10065.
Cold Spring Harb Perspect Biol. 2018 Jul 2;10(7):a033589. doi: 10.1101/cshperspect.a033589.
Specialized groups of neurons in the brain are key mediators of circadian rhythms, receiving daily environmental cues and communicating those signals to other tissues in the organism for entrainment and to organize circadian physiology. In , the "circadian clock" is housed in seven neuronal clusters, which are defined by their expression of the main circadian proteins, Period, Timeless, Clock, and Cycle. These clusters are distributed across the fly brain and are thereby subject to the respective environments associated with their anatomical locations. While these core components are universally expressed in all neurons of the circadian network, additional regulatory proteins that act on these components are differentially expressed, giving rise to "local clocks" within the network that nonetheless converge to regulate coherent behavioral rhythms. In this review, we describe the communication between the neurons of the circadian network and the molecular differences within neurons of this network. We focus on differences in protein-expression patterns and discuss how such variation can impart functional differences in each local clock. Finally, we summarize our current understanding of how communication within the circadian network intersects with intracellular biochemical mechanisms to ultimately specify behavioral rhythms. We propose that additional efforts are required to identify regulatory mechanisms within each neuronal cluster to understand the molecular basis of circadian behavior.
大脑中的特定神经元群是昼夜节律的关键调节者，它们接收日常环境线索，并将这些信号传递给生物体中的其他组织，以进行同步和组织昼夜生理节律。在，“生物钟”位于七个神经元簇中，这些神经元簇通过表达主要的昼夜节律蛋白 Period、Timeless、Clock 和 Cycle 来定义。这些簇分布在苍蝇大脑中，因此受到与其解剖位置相关的各自环境的影响。虽然这些核心成分普遍存在于昼夜节律网络中的所有神经元中，但对这些成分起作用的额外调节蛋白的表达是不同的，从而在网络内产生“局部时钟”，但这些时钟仍会聚以调节一致的行为节律。在这篇综述中，我们描述了昼夜节律网络中的神经元之间的通讯以及该网络中神经元内的分子差异。我们专注于蛋白质表达模式的差异，并讨论这种差异如何在每个局部时钟中产生功能差异。最后，我们总结了我们目前对昼夜节律网络内的通讯如何与细胞内生化机制相交织，最终确定行为节律的理解。我们提出，需要进一步努力识别每个神经元簇内的调节机制，以了解昼夜行为的分子基础。
