What rest in flies can tell us about sleep in mammals.

In addition to potentially providing insights into the molecular/biochemical basis of the restorative process, parallel studies of rest in Drosophila and sleep in mammals may provide candidate genes to assess in population genetic studies of sleep disorders and even in normal sleep (Figure 1Figure 1). A genetic basis is suspected for a number of human sleep disorders including both advanced sleep phase (Jones et al. 1999xJones, C.R., Campbell, S.S., Zone, S.E., Cooper, F., DeSano, A., Murphy, P.J., Jones, B., Czajkowski, L., and Ptacek, L.J. Nat. Med. 1999; 5: 1062–1065Crossref | PubMed | Scopus (335)See all ReferencesJones et al. 1999) and delayed sleep phase (Fink and Ancoli-Israel 1997xFink, R. and Ancoli-Israel, S. Sleep Res. 1997; 26: 713See all ReferencesFink and Ancoli-Israel 1997) syndromes, restless legs syndrome (Lazzarini et al. 1999xLazzarini, A., Walters, A.S., Hickey, K., Coccagna, G., Lugaresi, E., Ehrenberg, B.L., Picchietti, D.L., Brin, M.F., Stenroos, E.S., Verrico, T., and Johnson, W.G. Mov. Disord. 1999; 14: 111–116Crossref | PubMed | Scopus (84)See all ReferencesLazzarini et al. 1999), and narcolepsy (Mignot 1998xMignot, E. Neurology. 1998; 50: S16–S22Crossref | PubMedSee all ReferencesMignot 1998). Identification of the autosomal recessive mutation in canine narcolepsy as a defect in the hypocretin receptor 2 gene (Lin et al. 1999xLin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P.J., Nishino, S., and Mignot, E. Cell. 1999; 98: 365–376Abstract | Full Text | Full Text PDF | PubMed | Scopus (1696)See all ReferencesLin et al. 1999) and the narcoleptic-like phenotype of mice with a null mutation in the ligand for this receptor (Chemelli et al. 1999xChemelli, R.M., Willie, J.T., Sinton, C.M., Elmquist, J.K., Scammell, T., Lee, C., Richardson, J.A., Williams, S.C., Xiong, Y., Kisanuki, Y. et al. Cell. 1999; 98: 437–451Abstract | Full Text | Full Text PDF | PubMed | Scopus (1960)See all ReferencesChemelli et al. 1999) has encouraged researchers that understanding the genetic basis for human sleep disorders may be tractable.As in animal studies, certain aspects of normal sleep and the EEG appear to be highly heritable. Twin studies have demonstrated a genetic component in the occurrence of stages 2 and 4 and delta sleep, but not REM sleep (Linkowski 1999xLinkowski, P. J. Sleep Res. Suppl. 1999; 8: 11–13Crossref | PubMed | Scopus (74)See all ReferencesLinkowski 1999). A linkage marker for low-voltage alpha EEG has been identified on human chromosome 20q (Steinlein et al. 1992xSteinlein, O., Anokhin, A., Yping, M., Schalt, E., and Vogel, F. Genomics. 1992; 12: 69–73Crossref | PubMed | Scopus (80)See all ReferencesSteinlein et al. 1992). A study of 213 twin pairs determined the averaged heritabilites for the delta, theta, alpha, and beta frequencies of the EEG to be 76%, 89%, 89%, and 86%, respectively, indicating that brain electrical activity is one of the most heritable characteristics in humans (van Beijsterveldt et al. 1996xvan Beijsterveldt, C.E., Molenaar, P.C., de Geus, E.J., and Boomsma, D.I. Am. J. Hum. Genet. 1996; 58: 562–573PubMedSee all Referencesvan Beijsterveldt et al. 1996). Whether there is a genetic component to the propensity for habitually long (>9 hr) versus short (<5 hr) sleep (Aeschbach et al. 1996xAeschbach, D., Cajochen, C., Landolt, H., and Borbely, A.A. Am. J. Physiol. 1996; 270: R41–R53PubMedSee all ReferencesAeschbach et al. 1996) remains to be determined. Candidate genes to study in association with these and other aspects of normal sleep may arise from studies of rest in Drosophila.Taken together, these two papers (8xHendricks, J.C., Finn, S.M., Panckeri, K.A., Chavkin, J., Williams, J.A., Sehgal, A., and Pack, A.I. Neuron. 2000; 25: 129–138Abstract | Full Text | Full Text PDF | PubMedSee all References, 16xShaw, P.J., Cirelli, C., Greenspan, R.J., and Tononi, G. Science. 2000; 287: 1834–1837Crossref | PubMed | Scopus (505)See all References) illustrate how behavioral, pharmacological, molecular, and genetic approaches can be used to determine features of rest in Drosophila that are similar to mammalian sleep. These studies likely herald a new era for sleep research in which a model organism with well-established genetics will contribute valuable information relevant to the function and control of sleep in mammals. Such studies may thus enlighten one of the fundamental mysteries of neuroscience: how and, ultimately, why we sleep.*E-mail: thomas.kilduff@sri.com