Lethargus is a Caenorhabditis elegans sleep-like state

There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep- like states are evolutionarily ancient(1-3). The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults(4). Like sleep, lethargus maintains a constant temporal relationship with the expression of the C. elegans Period homologue LIN-42 ( ref. 5). Here we show that quiescence associated with lethargus has the additional sleep- like properties of reversibility, reduced responsiveness and homeostasis. We identify the cGMP-dependent protein kinase ( PKG) gene egl- 4 as a regulator of sleep-like behaviour, and show that egl- 4 functions in sensory neurons to promote the C. elegans sleep- like state. Conserved effects on sleep- like behaviour of homologous genes in C. elegans and Drosophila suggest a common genetic regulation of sleep- like states in arthropods and nematodes. Our results indicate that C. elegans is a suitable model system for the study of sleep regulation. The association of this C. elegans sleep- like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes.