GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333749/primaryOK200TranscriptomicsDrosophila melanogasterExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333749GEOGSEfalseGlia underlies brain wide activation and sleep behavior during sickness through adrenergic-glutamatergic axisSickness induces coordinated changes in physiology and behavior, including increased sleep, and despite specific circuits responsible for some of them have been recently described, how the brain orchestrates this global state shift remains unclear. 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.2026/06/02GSE333749GSM9772177GSM977217625244333749Drosophila melanogaster