Glia underlies brain wide activation and sleep behavior during sickness through adrenergic-glutamatergic axis

Whole-brain-single-cell RNA sequencing in a Drosophila model of sickness revealed that glia, rather than neurons, undergo the most extensive transcriptional remodeling and follow up experiments uncovered a neuron-glia axis that drives sickness sleep behavior.

Specifically, the process requires octopaminergic signaling in ensheathing glia (EG) and it is required for a coupled wave of glial and neuronal activation across the brain. EG gap junction functional coupling facilitates brain wide activation, which ultimately promotes sickness behavior through glutamatergic signaling. Altogether, these findings elevate glia from passive supporters to active coordinators of sickness behavior, opening new avenues for understanding the neuromodulatory basis of behavioral state drifts sleep, fatigue, and malaise.