Dynamics of a sleep homeostat observed in glia during behavior

An animal’s need to sleep grows with time spent awake and decays again during sleep. In the brain, a homeostatic process or signal has been proposed to represent sleep need, steadily increasing during wakefulness and gradually decreasing during sleep[1][1],[2][2]. However, such dynamics of a sleep homeostat, capturing the changing need to sleep in real time depending on behavior, has so far not been observed in identified cells[3][3]–[6][4]. Here, using a system that we developed for monitoring calcium activity over multiple days in head-fixed, walking fruit flies[7][5],[8][6], we find that a class of glia in the fly brain, called ensheathing glia[9][7]–[11][8], shows dynamics expected of a sleep homeostat. Calcium levels in these cells – monitored in a central brain area important for memory, navigation and sleep – integrate activity during wakefulness, reset during sleep, and saturate under sleep deprivation. Optogenetic activation of ensheathing glia induces sleep consistent with charging of the homeostat. The dynamics of the sleep homeostat, observed in glia of different brain compartments with similar but distinct dynamics, agree with conceptual model expectations[1][1],[2][2],[12][9],[13][10]. Ensheathing glia therefore act as a system for sleep control distributed across brain areas. The structural arrangement of these glia suggests that sleep homeostasis differentially impacts large ensembles of cells at the same time. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-6 [5]: #ref-7 [6]: #ref-8 [7]: #ref-9 [8]: #ref-11 [9]: #ref-12 [10]: #ref-13