4.8 Article

Intrinsic maturation of sleep output neurons regulates sleep ontogeny in Drosophila

Journal

CURRENT BIOLOGY
Volume 32, Issue 18, Pages 4025-+

Publisher

CELL PRESS
DOI: 10.1016/j.cub.2022.07.054

Keywords

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Funding

  1. NIH [DP2NS111996, R56NS109144, R01NS120979, T32HL07953, R21MH123841, R01AG071818]
  2. Burroughs Wellcome Career Award for Medical Scientists
  3. 2020 Max Planck Humboldt Research Award
  4. NSF [CPS2038873]
  5. Honda Research Institute

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The study reveals that the transcriptional states of sleep output neurons play a crucial role in the changes in sleep across the lifespan in fruit flies.
The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenom-enon. 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 mela-nogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-inva-sive 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 impli-cate 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.

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