An AP2 transcription factor is required for a sleep-active neuron to induce sleep-like quiescence in C. elegans

Curr Biol. 2013 Nov 18;23(22):2215-2223. doi: 10.1016/j.cub.2013.09.028. Epub 2013 Oct 31.


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.

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / physiology*
  • Gene Expression Regulation
  • Interneurons / metabolism
  • Larva
  • Locomotion
  • Mutation
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Signal Transduction
  • Sleep / physiology
  • Transcription Factor AP-2 / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Caenorhabditis elegans Proteins
  • Neuropeptides
  • Transcription Factor AP-2
  • gamma-Aminobutyric Acid