Lee Han S, Billings Heather J, Lehman Michael N
Department of Cell Biology, Neurobiology and Anatomy, Neuroscience Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0521, USA.
J Biol Rhythms. 2003 Dec;18(6):435-49. doi: 10.1177/0748730403259106.
Although impressive progress has been made in understanding the molecular basis of pacemaker function in the suprachiasmatic nucleus (SCN), fundamental questions about cellular and regional heterogeneity within the SCN, and how this heterogeneity might contribute to SCN pacemaker function at a tissue level, have remained unresolved. To reexamine cellular and regional heterogeneity within the SCN, the authors have focused on two key questions: which SCN cells are endogenously rhythmic and/or directly light responsive? Observations of endogenous rhythms of electrical activity, gene/protein expression, and protein phosphorylation suggest that the SCN in mammals examined to date is composed of anatomically distinct rhythmic and nonrhythmic components. Endogenously rhythmic neurons are primarily found in rostral, dorsomedial, and ventromedial portions of the nucleus; at mid and caudal levels, the distribution of endogenously rhythmic cells in the SCN has the appearance of a "shell." The majority of nonrhythmic cells, by contrast, are located in a central "core" region of the SCN, which is complementary to the shell. The location of light-responsive cells, defined by direct retinohypothalamic input and light-induced gene expression, largely overlaps the location of nonrhythmic cells in the SCN core, although, in hamsters and mice light-responsive cells are also present in the ventral portion of the rhythmic shell. While the relative positions of rhythmic and light-responsive components of the SCN are similar between species, the precise boundaries of these components, and neurochemical phenotype of cells within them, are variable. Intercellular communication between these components may be a key feature responsible for the unique pacemaker properties of the SCN observed at a tissue and whole animal level.
尽管在理解视交叉上核（SCN）起搏器功能的分子基础方面已经取得了令人瞩目的进展，但关于SCN内细胞和区域异质性的基本问题，以及这种异质性如何在组织水平上对SCN起搏器功能产生影响，仍未得到解决。为了重新审视SCN内的细胞和区域异质性，作者聚焦于两个关键问题：哪些SCN细胞具有内源性节律和/或直接对光有反应？对电活动、基因/蛋白质表达和蛋白质磷酸化的内源性节律的观察表明，迄今为止所研究的哺乳动物的SCN由解剖学上不同的节律性和非节律性成分组成。内源性节律性神经元主要存在于该核的前部、背内侧和腹内侧部分；在中部和尾部水平，SCN内源性节律性细胞的分布呈现出“壳”的外观。相比之下，大多数非节律性细胞位于SCN的中央“核心”区域，该区域与“壳”互补。由直接的视网膜下丘脑输入和光诱导基因表达所定义的光反应性细胞的位置，在很大程度上与SCN核心中非节律性细胞的位置重叠，不过，在仓鼠和小鼠中，光反应性细胞也存在于节律性“壳”的腹侧部分。虽然SCN节律性和光反应性成分的相对位置在不同物种之间相似，但这些成分的精确边界以及其中细胞的神经化学表型是可变的。这些成分之间的细胞间通讯可能是在组织和全动物水平上观察到的SCN独特起搏器特性的关键特征。
