title: Neuronal machinery of sleep homeostasis in Drosophila.
abstract: Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila's sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c.
authors.affiliation: Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Donlea
authors.affiliation: Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Diogo
authors.initials: D
authors.lastname: Pimentel
authors.affiliation: Centre for Neural Circuits and Behaviour, University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK. Electronic address: gero.miesenboeck@cncb.ox.ac.uk.
authors.forename: Gero
authors.initials: G
authors.lastname: Miesenböck
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D012890:Sleep / Q000235:genetics*; D012892:Sleep Deprivation / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; C502709:cv-c protein, Drosophila; C085379:rho GTPase-activating protein