Dynamics of sleep, feeding, and metabolic homeostasis in Drosophila ensheathing glia, astrocytes, and neurons

Abstract Sleep is critical for homeostatic processes in the brain, including metabolism and waste removal. Here, we identify brain-wide, locally acting sleep homeostats for the short, naturally occurring sleep bouts of Drosophila in the two major classes of glia that arborize inside the brain, astrocytes and ensheathing glia. We show that glia surround respiratory tracheal tubes, that the metabolic gas carbon dioxide, changes in pH, or behavioral activity, all induce long lasting calcium responses, and that astrocytes and glia show circadian calcium modulations. Glia describe sleep homeostasis in behaving flies more faithfully than previously identified sleep circuits in the central complex, but a subset of neurons in the fan-shaped body is important for feeding homeostasis. Local optogenetic activation of astrocytes or ensheathing glia is sufficient to induce sleep. Together, glia calcium levels can be modeled as homeostatic controllers of metabolic activity, thus establishing a link between metabolism and sleep.