Intrinsic maturation of sleep output neurons regulates sleep ontogeny in Drosophila

The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared with mature sleep with regard to sleep states. How the intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate the changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dorsal fan-shaped body (dFB) suggest that these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate the genes involved in dFB sleep circuit maturation. These results reveal that the dynamic transcriptional states of sleep output neurons contribute to the changes in sleep across the lifespan.