Smyllie Nicola J, Hastings Michael H, Patton Andrew P
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Neuroscientist. 2025 Feb;31(1):65-79. doi: 10.1177/10738584241245307. Epub 2024 Apr 11.
Almost every facet of our behavior and physiology varies predictably over the course of day and night, anticipating and adapting us to their associated opportunities and challenges. These rhythms are driven by endogenous biological clocks that, when deprived of environmental cues, can continue to oscillate within a period of approximately 1 day, hence -. Normally, retinal signals synchronize them to the cycle of light and darkness, but disruption of circadian organization, a common feature of modern lifestyles, carries considerable costs to health. Circadian timekeeping pivots around a cell-autonomous molecular clock, widely expressed across tissues. These cellular timers are in turn synchronized by the principal circadian clock of the brain: the hypothalamic suprachiasmatic nucleus (SCN). Intercellular signals make the SCN network a very powerful pacemaker. Previously, neurons were considered the sole SCN timekeepers, with glial cells playing supportive roles. New discoveries have revealed, however, that astrocytes are active partners in SCN network timekeeping, with their cell-autonomous clock regulating extracellular glutamate and GABA concentrations to control circadian cycles of SCN neuronal activity. Here, we introduce circadian timekeeping at the cellular and SCN network levels before focusing on the contributions of astrocytes and their mutual interaction with neurons in circadian control in the brain.
我们行为和生理的几乎每个方面在白天和黑夜的过程中都有可预测的变化,使我们能够预期并适应与之相关的机遇和挑战。这些节律由内源性生物钟驱动,当生物钟被剥夺环境线索时,仍可在大约1天的周期内继续振荡,因此——。通常,视网膜信号会使其与昼夜循环同步,但昼夜节律紊乱是现代生活方式的一个常见特征,会给健康带来相当大的代价。昼夜计时围绕着一个细胞自主分子钟展开,该分子钟在各种组织中广泛表达。这些细胞定时器又由大脑的主要昼夜节律钟——下丘脑视交叉上核(SCN)同步。细胞间信号使SCN网络成为一个非常强大的起搏器。以前,神经元被认为是唯一的SCN计时细胞,神经胶质细胞起支持作用。然而,新的发现表明,星形胶质细胞是SCN网络计时的活跃伙伴,其细胞自主时钟调节细胞外谷氨酸和GABA浓度,以控制SCN神经元活动的昼夜节律周期。在此,我们先介绍细胞和SCN网络水平的昼夜计时,然后重点探讨星形胶质细胞在大脑昼夜控制中的贡献及其与神经元的相互作用。