title: An AP2 transcription factor is required for a sleep-active neuron to induce sleep-like quiescence in C. elegans.
abstract: BACKGROUND
  Sleep is an essential behavior that is found in all animals that have a nervous system. Neural activity is thought to control sleep, but little is known about the identity and the function of neural circuits underlying sleep. Lethargus is a developmentally regulated period of behavioral quiescence in C. elegans larvae that has sleep-like properties.
  
  
  RESULTS
  We studied sleep-like behavior in C. elegans larvae and found that it requires a highly conserved AP2 transcription factor, aptf-1, which was expressed strongly in only five interneurons in the head. Expression of aptf-1 in one of these neurons, the GABAergic neuron RIS, was required for quiescence. RIS was strongly and acutely activated at the transition from wake-like to sleep-like behavior. Optogenetic activation of aptf-1-expressing neurons ectopically induced acute behavioral quiescence in an aptf-1-dependent manner. RIS ablation caused a dramatic reduction of quiescence. RIS-dependent quiescence, however, does not require GABA but requires neuropeptide signaling.
  
  
  CONCLUSIONS
  We conclude that RIS acts as a sleep-active, sleep-promoting neuron that requires aptf-1 to induce sleep-like behavior through neuropeptide signaling. Sleep-promoting GABAergic-peptidergic neurons have also been identified in vertebrate brains, suggesting that common circuit principles exist between sleep in vertebrates and sleep-like behavior in invertebrates.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Turek
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Lewandrowski
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Goettingen, Germany. Electronic address: henrik.bringmann@mpibpc.mpg.de.
authors.forename: Henrik
authors.initials: H
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D007395:Interneurons / Q000378:metabolism; D007814:Larva; D008124:Locomotion; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D015398:Signal Transduction; D012890:Sleep / Q000502:physiology; D050656:Transcription Factor AP-2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D009479:Neuropeptides; D050656:Transcription Factor AP-2; D005680:gamma-Aminobutyric Acid