Dynamics of glia and neurons regulate homeostatic rest, sleep and feeding behavior in Drosophila

Abstract Homeostatic processes, including sleep, are critical for brain function. Here we identify astrocyte-like glia (or astrocytes, AL) and ensheathing glia (EG), the two major classes of glia that arborize inside the brain, as brain-wide, locally acting homeostats for the short, naturally occurring rest and sleep bouts of Drosophila , and show that a subset of neurons in the fan-shaped body encodes feeding homeostasis. We show that the metabolic gas carbon dioxide, changes in pH and behavioral activity all induce long-lasting calcium responses in EG and AL, and that calcium levels in both glia types show circadian modulation. The homeostatic dynamics of these glia can be modeled based on behavior. Additionally, local optogenetic activation of AL or EG is sufficient to induce rest. Together, these results suggest that glial calcium levels are homeostatic controllers of metabolic activity, thus establishing a link between metabolism, rest and sleep.