Ness Natalie, Díaz-Clavero Sandra, Hoekstra Marieke M B, Brancaccio Marco
Department of Brain Science, Imperial College London, London, UK.
UK Dementia Research Institute at Imperial College London, London, UK.
EMBO J. 2025 Jan;44(2):356-381. doi: 10.1038/s44318-024-00324-w. Epub 2024 Dec 2.
Astrocytes of the suprachiasmatic nucleus (SCN) can regulate sleep-wake cycles in mammals. However, the nature of the information provided by astrocytes to control circadian patterns of behavior is unclear. Neuronal circadian activity across the SCN is organized into spatiotemporal waves that govern seasonal adaptations and timely engagement of behavioral outputs. Here, we show that astrocytes across the mouse SCN exhibit instead a highly uniform, pulse-like nighttime activity. We find that rhythmic astrocytic GABA production via polyamine degradation provides an inhibitory nighttime tone required for SCN circuit synchrony, thereby acting as an internal astrocyte zeitgeber (or "astrozeit"). We further identify synaptic GABA and astrocytic GABA as two key players underpinning coherent spatiotemporal circadian patterns of SCN neuronal activity. In describing a new mechanism by which astrocytes contribute to circadian timekeeping, our work provides a general blueprint for understanding how astrocytes encode temporal information underlying complex behaviors in mammals.
视交叉上核（SCN）的星形胶质细胞可调节哺乳动物的睡眠-觉醒周期。然而，星形胶质细胞提供的用于控制昼夜节律行为模式的信息的本质尚不清楚。整个SCN的神经元昼夜活动被组织成时空波，这些时空波控制着季节性适应和行为输出的适时参与。在这里，我们发现小鼠SCN中的星形胶质细胞呈现出高度一致的、类似脉冲的夜间活动。我们发现，通过多胺降解产生的节律性星形胶质细胞GABA提供了SCN回路同步所需的夜间抑制性调节，从而充当内部星形胶质细胞授时因子（或“astrozeit”）。我们进一步确定突触GABA和星形胶质细胞GABA是支撑SCN神经元活动连贯时空昼夜节律模式的两个关键因素。在描述星形胶质细胞对昼夜节律计时的一种新机制时，我们的工作为理解星形胶质细胞如何编码哺乳动物复杂行为背后的时间信息提供了一个总体蓝图。
