Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, East Spokane Falls Boulevard, Spokane, WA 99202, USA.
Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, East Spokane Falls Boulevard, Spokane, WA 99202, USA; Department of Mathematics and Computer Science, Whitworth University, West Hawthorne Road, Spokane, WA 99251, USA.
Curr Biol. 2020 Nov 16;30(22):4373-4383.e7. doi: 10.1016/j.cub.2020.08.052. Epub 2020 Sep 24.
Mammalian sleep expression and regulation have historically been thought to reflect the activity of neurons. Changes in other brain cells (glia) across the sleep-wake cycle and their role in sleep regulation are comparatively unexplored. We show that sleep and wakefulness are accompanied by state-dependent changes in astroglial activity. Using a miniature microscope in freely behaving mice and a two-photon microscope in head-fixed, unanesthetized mice, we show that astroglial calcium signals are highest in wake and lowest in sleep and are most pronounced in astroglial processes. We also find that astroglial calcium signals during non-rapid eye movement sleep change in proportion to sleep need. In contrast to neurons, astrocytes become less synchronized during non-rapid eye movement sleep after sleep deprivation at the network and single-cell level. Finally, we show that conditionally reducing intracellular calcium in astrocytes impairs the homeostatic response to sleep deprivation. Thus, astroglial calcium activity changes dynamically across vigilance states, is proportional to sleep need, and is a component of the sleep homeostat.
哺乳动物的睡眠表现和调节一直被认为反映了神经元的活动。然而，在睡眠-觉醒周期中，其他脑细胞（神经胶质细胞）的变化及其在睡眠调节中的作用还比较未知。我们发现，睡眠和觉醒伴随着星形胶质细胞活动的状态依赖性变化。我们使用自由活动的小鼠微型显微镜和头部固定、未麻醉的小鼠双光子显微镜，表明星形胶质细胞钙信号在觉醒时最高，在睡眠时最低，并且在星形胶质细胞突起中最为明显。我们还发现，在非快速眼动睡眠期间，星形胶质细胞钙信号的变化与睡眠需求成比例。与神经元不同，在睡眠剥夺后的非快速眼动睡眠期间，星形胶质细胞在网络和单细胞水平上的同步性降低。最后，我们表明，条件性地减少星形胶质细胞内的钙会损害对睡眠剥夺的稳态反应。因此，星形胶质细胞钙活性在警觉状态下动态变化，与睡眠需求成比例，并且是睡眠稳态的组成部分。
