Serviere J
Laboratoire de Physiologie Sensorielle, INRA, Jouy-en Josas.
C R Seances Soc Biol Fil. 1998;192(4):683-710.
The focus of the present review is to present recent studies of the mammalian circadian clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The main questions in circadian neuroscience are: how many oscillators are implicated, how are their daily oscillations generated and synchronized to the external environment and how does the central clock send timed signals to the whole organism. The review is introduced by a presentation of circadian system properties and by a description of the responses to manipulations of the main entraining factor, i.e. the light-dark cycle. The anatomy of the SCN and its major afferents from the retina (glutamate, Substance P), raphe (serotonin) and intergeniculate leaflet (neuropeptide Y) of the thalamus are presented with a special emphasis on the interaction of these inputs with the circadian timekeeping mechanism. The arguments related to the issue of whether the retina contain an endogenous oscillator are exposed. What is known of the endogenous mechanism(s) of this small structure containing 10,000 or so "self-oscillating neurons" is reviewed through: i) the anatomical distribution and functional significance of clock-peptides (VIP, PHI, GRP, VP or SS), ii) the putative involvement of the SCN astrocytic population in coordinating neuronal activities, iii) the various aspects of cellular activity (electrical activity, energy metabolism, protein or peptide synthesis) and iv) the participation of immediate early genes in light-driven phase shifts. The present understanding of molecular timekeeping mechanism is exposed in light of the growing list of candidate clock-genes described within the SCN as well as in peripheral tissues of mammals and also in the clock-systems of phylogenetically lower species. Efferents from the SCN are also discussed with an interest toward understanding how the central circadian information is transmitted to the rest of the brain in order to impulse or/and coordinate the numerous rhythmic activities of the organism. Finally, cellular disturbances in peptide expression or content, reduction in the amplitude of a given functional index or even astrocytic proliferation are viewed along the line of pathologies observed with aging.
本综述的重点是介绍关于位于下丘脑视交叉上核（SCN）的哺乳动物生物钟的最新研究。昼夜节律神经科学中的主要问题包括：涉及多少个振荡器，它们的日常振荡是如何产生并与外部环境同步的，以及中央时钟如何向整个生物体发送定时信号。综述开篇介绍了昼夜节律系统的特性，并描述了对主要同步因子即明暗周期操纵的反应。介绍了SCN的解剖结构及其来自视网膜（谷氨酸、P物质）、中缝核（5-羟色胺）和丘脑间膝叶（神经肽Y）的主要传入神经，特别强调了这些输入与昼夜计时机制的相互作用。阐述了与视网膜是否含有内源性振荡器这一问题相关的论据。通过以下方面综述了对这个包含约10000个“自振荡神经元”的小结构的内源性机制的了解：i）生物钟肽（血管活性肠肽、肽组氨酸异亮氨酸肽、胃泌素释放肽、血管加压素或生长抑素）的解剖分布和功能意义；ii）SCN星形胶质细胞群体在协调神经元活动中的假定作用；iii）细胞活动的各个方面（电活动、能量代谢、蛋白质或肽合成）；iv）即刻早期基因在光驱动相移中的参与。鉴于在SCN以及哺乳动物外周组织中描述的候选生物钟基因不断增加，同时也鉴于系统发育较低物种的生物钟系统，阐述了目前对分子计时机制的理解。还讨论了SCN的传出神经，旨在了解中央昼夜节律信息如何传递到大脑其他部分，以驱动或/和协调生物体的众多节律活动。最后，沿着衰老过程中观察到的病理学方向，审视了肽表达或含量的细胞紊乱、给定功能指标振幅的降低甚至星形胶质细胞的增殖。
