Notch Signaling Modulates Sleep Homeostasis and Learning after Sleep Deprivation in Drosophila

• Published in: Current biology 2011-05, Vol.21 (10), p.835-840
• Main Authors: Seugnet, Laurent, Suzuki, Yasuko, Merlin, Gabriel, Gottschalk, Laura, Duntley, Stephen P., Shaw, Paul J.
• Format: Article
• Language: English
• Subjects: Adult; adults; Analysis of Variance; Animals; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila - physiology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; gene expression regulation; gene overexpression; homeostasis; Homeostasis - physiology; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; learning; Learning - physiology; Life Sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microscopy, Confocal; mushroom bodies; Mushroom Bodies - metabolism; mutants; mutation; Mutation - genetics; Neuroglia - metabolism; neurons; Neurons - metabolism; Polymerase Chain Reaction; Receptors, Notch - metabolism; signal transduction; Signal Transduction - physiology; Sleep - physiology; sleep deprivation; transgenes
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2011.04.001

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 Notchspl-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. ► Mutations in bunched, a regulator of Notch, affect sleep homeostasis ► Notch signaling can alter sleep homeostasis and sleep loss-induced learning deficits ► Notch is present in glial processes; Delta is predominantly in neuronal cell bodies ► Notch mediates a neuron-glia pathway involved in sleep and learning