TY - JOUR
T1 - Notch signaling modulates sleep homeostasis and learning after sleep deprivation in drosophila
AU - Seugnet, Laurent
AU - Suzuki, Yasuko
AU - Merlin, Gabriel
AU - Gottschalk, Laura
AU - Duntley, Stephen P.
AU - Shaw, Paul J.
N1 - Funding Information:
We thank Matthew Thimgan for helpful comments. This study was funded in part by National Institutes of Health (NIH) grants 1 R01 NS051305-01A1 and 5 K07 AG21164-02, the McDonnell Center for Cellular and Molecular Neurobiology, and NIH Neuroscience Blueprint Core Grant NS057105.
PY - 2011/5/24
Y1 - 2011/5/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79957502385&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2011.04.001
DO - 10.1016/j.cub.2011.04.001
M3 - Article
C2 - 21549599
AN - SCOPUS:79957502385
SN - 0960-9822
VL - 21
SP - 835
EP - 840
JO - Current Biology
JF - Current Biology
IS - 10
ER -