Nature 451, 569-572 (31 January 2008) | doi:10.1038/nature06535; Received 21 August 2007; Accepted 13 December 2007; Published online 9 January 2008

Lethargus is a Caenorhabditis elegans sleep-like state

David M. Raizen1,2, John E. Zimmerman1, Matthew H. Maycock1, Uyen D. Ta1,2, Young-jai You5, Meera V. Sundaram3 & Allan I. Pack1,4

  1. Center for Sleep and Respiratory Neurobiology,
  2. Department of Neurology,
  3. Department of Genetics,
  4. Division of Sleep Medicine, Department of Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA
  5. Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA

Correspondence to: David M. Raizen1,2 Correspondence and requests for materials should be addressed to D.M.R. (Email: raizen@mail.med.upenn.edu).

There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep-like states are evolutionarily ancient1, 2, 3. The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults4. 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.


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