title: Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila.
abstract: The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis. Combining bunched and Delta loss-of-function mutations rescues normal homeostasis, suggesting that Notch signaling may be involved in regulating sensitivity to sleep loss. Preventing the downregulation of Delta by overexpressing a wild-type transgene in MBs reduces sleep homeostasis and, importantly, prevents learning impairments induced by sleep deprivation. Similar resistance to sleep loss is observed with Notch(spl-1) gain-of-function mutants. Immunohistochemistry reveals that the Notch receptor is expressed in glia, whereas Delta is localized in neurons. Importantly, the expression in glia of the intracellular domain of Notch, a dominant activated form of the receptor, is sufficient to prevent learning deficits after sleep deprivation. Together, these results identify a novel neuron-glia signaling pathway dependent on Notch and regulated by bunched. These data highlight the emerging role of neuron-glia interactions in regulating both sleep and learning impairments associated with sleep loss.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8108, St. Louis, MO 63110, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Seugnet
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Gabriel
authors.initials: G
authors.lastname: Merlin
authors.forename: Laura
authors.initials: L
authors.lastname: Gottschalk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Duntley
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D024521:Mushroom Bodies / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012890:Sleep / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; C529273:bun protein, Drosophila; C064045:delta protein