title: Octopamine regulates sleep in drosophila through protein kinase A-dependent mechanisms.
abstract: Sleep is a fundamental process, but its regulation and function are still not well understood. The Drosophila model for sleep provides a powerful system to address the genetic and molecular mechanisms underlying sleep and wakefulness. Here we show that a Drosophila biogenic amine, octopamine, is a potent wake-promoting signal. Mutations in the octopamine biosynthesis pathway produced a phenotype of increased sleep, which was restored to wild-type levels by pharmacological treatment with octopamine. Moreover, electrical silencing of octopamine-producing cells decreased wakefulness, whereas excitation of these neurons promoted wakefulness. Because protein kinase A (PKA) is a putative target of octopamine signaling and is also implicated in Drosophila sleep, we investigated its role in the effects of octopamine on sleep. We found that decreased PKA activity in neurons rendered flies insensitive to the wake-promoting effects of octopamine. However, this effect of PKA was not exerted in the mushroom bodies, a site previously associated with PKA action on sleep. These studies identify a novel pathway that regulates sleep in Drosophila.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Crocker
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D024521:Mushroom Bodies / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009655:Octopamine / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000235:genetics*; D014439:Tyramine / Q000378:metabolism; D014445:Tyrosine Decarboxylase / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D049452:Green Fluorescent Proteins; D009655:Octopamine; D017868:Cyclic AMP-Dependent Protein Kinases; C500802:Tdc2 protein, Drosophila; D014445:Tyrosine Decarboxylase; D009638:Norepinephrine; D014439:Tyramine
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