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

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.

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.

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.