Notch signaling modulates sleep homeostasis and learning after sleep deprivation in drosophila

Laurent Seugnet, Yasuko Suzuki, Gabriel Merlin, Laura Gottschalk, Stephen P. Duntley, Paul J. Shaw

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)835-840
Number of pages6
JournalCurrent Biology
Volume21
Issue number10
DOIs
StatePublished - May 24 2011

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