The NALCN channel complex is necessary for stabilizing sleep in Caenorhabditis elegans

Sleep is a fundamental physiological state that is widely conserved across diverse animal species. Caenorhabditis elegans exhibits developmentally timed sleep (DTS) and stress-induced sleep (SIS), which meet the behavioral definition of sleep and are regulated by molecular mechanisms shared with other animals. Here, we studied the sleep-regulating functions of UNC-80, which forms a complex with NCA-1 and NCA-2 (hereafter collectively referred to as NCA), and UNC-79. We found that the unc-80 loss-of-function (lf) mutants experienced lower quiescence and a more fragmented and longer DTS than the wild type. The unc-80(lf) mutants also showed lower quiescence during SIS immediately after heat stress, and fragmented SIS. After that, however, quiescence remained higher for a longer time, resulting in a higher total quiescence than observed in the wild type. Similar sleep defects were observed in nca(lf) and unc-79(lf) mutants, indicating that these genes have common functions in sleep regulation. Deprivation of SIS immediately after heat stress in the wild type resulted in a sleep pattern similar to that of the unc-80(lf) mutants, suggesting that sleep immediately after stress might be essential and thus is under strong homeostatic regulation and that the prolonged DTS and SIS of the unc-80(lf) mutants might be rebound sleep. Our findings elucidated that NCA, UNC-79, and UNC-80 are necessary for stabilizing sleep and suggest the importance of the early period of sleep.