Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reduced sleep in Drosophila Shaker mutants

Nature volume 434, pages 1087–1092 (2005)Cite this article

Abstract

Most of us sleep 7–8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3–4 h of sleep—a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Sleep in mns flies.
Figure 2: Response to sleep deprivation and measures of performance in mns flies.
Figure 3: The Shaker channel and the mns mutation.
Figure 4: Effects of outcrossing on daily sleep amount and longevity.

References

  1. Horne, J. A. Why we Sleep. The Functions of Sleep in Humans and Other Mammals (Oxford Univ. Press, Oxford, 1988)

    Google Scholar 

  2. Tobler, I. in Principles and Practice of Sleep Medicine (eds Kryger, M. H., Roth, T. & Dement, W. C.) 72–81 (W. B. Saunders, Philadelphia, 2000)

    Google Scholar 

  3. Rechtschaffen, A., Gilliland, M. A., Bergmann, B. M. & Winter, J. B. Physiological correlates of prolonged sleep deprivation in rats. Science 221, 182–184 (1983)

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Shaw, P. J., Tononi, G., Greenspan, R. J. & Robinson, D. F. Stress response genes protect against lethal effects of sleep deprivation in Drosophila . Nature 417, 287–291 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Van Dongen, H. P., Maislin, G., Mullington, J. M. & Dinges, D. F. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep 26, 117–126 (2003)

    Article  PubMed  Google Scholar 

  6. Borbely, A. A. & Achermann, P. Sleep homeostasis and models of sleep regulation. J. Biol. Rhythms 14, 557–568 (1999)

    CAS  PubMed  Google Scholar 

  7. Dijk, D. J. & Lockley, S. W. Integration of human sleep-wake regulation and circadian rhythmicity. J. Appl. Physiol. 92, 852–862 (2002)

    Article  PubMed  Google Scholar 

  8. Stanewsky, R. Genetic analysis of the circadian system in Drosophila melanogaster and mammals. J. Neurobiol. 54, 111–147 (2003)

    Article  CAS  PubMed  Google Scholar 

  9. Lowrey, P. L. & Takahashi, J. S. Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu. Rev. Genom. Hum. Genet. 5, 407–441 (2004)

    Article  CAS  Google Scholar 

  10. Konopka, R. J. & Benzer, S. Clock mutants of Drosophila melanogaster . Proc. Natl Acad. Sci. USA 68, 2112–2116 (1971)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bargiello, T. A., Jackson, F. R. & Young, M. W. Restoration of circadian behavioural rhythms by gene transfer in Drosophila . Nature 312, 752–754 (1984)

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Zehring, W. A. et al. P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster . Cell 39, 369–376 (1984)

    Article  CAS  PubMed  Google Scholar 

  13. Naylor, E. et al. The circadian clock mutation alters sleep homeostasis in the mouse. J. Neurosci. 20, 8138–8143 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wisor, J. P. et al. A role for cryptochromes in sleep regulation. BMC Neurosci. 3, 20 (doi:10.1186/1471-2202-3-20) (2002)

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kopp, C., Albrecht, U., Zheng, B. & Tobler, I. Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Eur. J. Neurosci. 16, 1099–1106 (2002)

    Article  PubMed  Google Scholar 

  16. Shiromani, P. J. et al. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R47–R57 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. Easton, A., Meerlo, P., Bergmann, B. & Turek, F. W. The suprachiasmatic nucleus regulates sleep timing and amount in mice. Sleep 27, 1307–1318 (2004)

    Article  PubMed  Google Scholar 

  18. Heath, A. C., Kendler, K. S., Eaves, L. J. & Martin, N. G. Evidence for genetic influences on sleep disturbance and sleep pattern in twins. Sleep 13, 318–335 (1990)

    Article  CAS  PubMed  Google Scholar 

  19. Linkowski, P. EEG sleep patterns in twins. J. Sleep Res. 8 (suppl. 1), 11–13 (1999)

    Article  PubMed  Google Scholar 

  20. Partinen, M., Kaprio, J., Koskenvuo, M., Putkonen, P. & Langinvainio, H. Genetic and environmental determination of human sleep. Sleep 6, 179–185 (1983)

    Article  CAS  PubMed  Google Scholar 

  21. Tafti, M. & Franken, P. Invited review: genetic dissection of sleep. J. Appl. Physiol. 92, 1339–1347 (2002)

    Article  PubMed  Google Scholar 

  22. Meddis, R., Pearson, A. J. & Langford, G. An extreme case of healthy insomnia. Electroencephalogr. Clin. Neurophysiol. 35, 213–214 (1973)

    Article  CAS  PubMed  Google Scholar 

  23. Jones, H. S. & Oswald, I. Two cases of healthy insomnia. Electroencephalogr. Clin. Neurophysiol. 24, 378–380 (1968)

    Article  CAS  PubMed  Google Scholar 

  24. Webb, W. B. Individual differences in sleep length. Int. Psychiatry Clin. 7, 44–47 (1970)

    CAS  PubMed  Google Scholar 

  25. Stuss, D. & Broughton, R. Extreme short sleep: personality profiles and a case study of sleep requirement. Waking Sleep. 2, 101–105 (1978)

    Google Scholar 

  26. Schenck, C. H. & Mahowald, M. W. Severe, childhood-onset, idiopathic, life-long insomnia responding selectively to opiate therapy: case report with 19 year follow-up. Sleep Med. 2, 531–536 (2001)

    Article  CAS  PubMed  Google Scholar 

  27. Cirelli, C. Searching for sleep mutants of Drosophila melanogaster . Bioessays 25, 940–949 (2003)

    Article  CAS  PubMed  Google Scholar 

  28. Hendricks, J. C. et al. Rest in Drosophila is a sleep-like state. Neuron 25, 129–138 (2000)

    Article  CAS  PubMed  Google Scholar 

  29. Shaw, P. J., Cirelli, C., Greenspan, R. J. & Tononi, G. Correlates of sleep and waking in Drosophila melanogaster . Science 287, 1834–1837 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Huber, R. et al. Sleep homeostasis in Drosophila melanogaster . Sleep 27, 628–639 (2004)

    Article  PubMed  Google Scholar 

  31. Cirelli, C., Gutierrez, C. M. & Tononi, G. Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron 41, 35–43 (2004)

    Article  CAS  PubMed  Google Scholar 

  32. Nitz, D. A., van Swinderen, B., Tononi, G. & Greenspan, R. J. Electrophysiological correlates of rest and activity in Drosophila melanogaster . Curr. Biol. 12, 1934–1940 (2002)

    Article  CAS  PubMed  Google Scholar 

  33. Rorth, P. et al. Systematic gain-of-function genetics in Drosophila . Development 125, 1049–1057 (1998)

    CAS  PubMed  Google Scholar 

  34. Spradling, A. C. et al. The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes. Genetics 153, 135–177 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Sutcliffe, J. G. & Milner, R. J. Alternative mRNA splicing: the Shaker gene. Trends Genet. 4, 297–299 (1988)

    Article  CAS  PubMed  Google Scholar 

  36. Schwarz, T. L., Tempel, B. L., Papazian, D. M., Jan, Y. N. & Jan, L. Y. Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila . Nature 331, 137–142 (1988)

    Article  ADS  CAS  PubMed  Google Scholar 

  37. Littleton, J. T. & Ganetzky, B. Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron 26, 35–43 (2000)

    Article  CAS  PubMed  Google Scholar 

  38. Walcourt, A., Scott, R. L. & Nash, H. A. Blockage of one class of potassium channel alters the effectiveness of halothane in a brain circuit of Drosophila . Anesth. Analg. 92, 535–541 (2001)

    Article  CAS  PubMed  Google Scholar 

  39. Rogero, O., Hammerle, B. & Tejedor, F. J. Diverse expression and distribution of Shaker potassium channels during the development of the Drosophila nervous system. J. Neurosci. 17, 5108–5118 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cuello, L. G., Cortes, D. M. & Perozo, E. Molecular architecture of the KvAP voltage-dependent K+ channel in a lipid bilayer. Science 306, 491–495 (2004)

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Li-Smerin, Y., Hackos, D. H. & Swartz, K. J. Alpha-helical structural elements within the voltage-sensing domains of a K+ channel. J. Gen. Physiol. 115, 33–50 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hendricks, J. C. et al. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster . J. Biol. Rhythms 18, 12–25 (2003)

    Article  CAS  PubMed  Google Scholar 

  43. Taheri, S. & Mignot, E. The genetics of sleep disorders. Lancet Neurol. 1, 242–250 (2002)

    Article  CAS  PubMed  Google Scholar 

  44. Hendricks, J. C. et al. A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nature Neurosci. 4, 1108–1115 (2001)

    Article  CAS  PubMed  Google Scholar 

  45. Benington, J. H., Woudenberg, M. C. & Heller, H. C. Apamin, a selective SK potassium channel blocker, suppresses REM sleep without a compensatory rebound. Brain Res. 692, 86–92 (1995)

    Article  CAS  PubMed  Google Scholar 

  46. Vyazovskiy, V. V. et al. Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2. Brain Res. 947, 204–211 (2002)

    Article  CAS  PubMed  Google Scholar 

  47. Espinosa, F., Marks, G., Heintz, N. & Joho, R. H. Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain Behav. 3, 90–100 (2004)

    Article  CAS  PubMed  Google Scholar 

  48. Liguori, R. et al. Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 124, 2417–2426 (2001)

    Article  CAS  PubMed  Google Scholar 

  49. Levine, J. D., Funes, P., Dowse, H. B. & Hall, J. C. Signal analysis of behavioral and molecular cycles. BMC Neurosci. 3, 1 (2002)

    Article  PubMed  PubMed Central  Google Scholar 

  50. Timpe, L. C. & Jan, L. Y. Gene dosage and complementation analysis of the Shaker locus in Drosophila . J. Neurosci. 7, 1307–1317 (1987)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the United States Defense Advanced Research Projects Agency. B.G. is funded by NIH. We thank C. Holladay for technical assistance, M. Heisenberg and his laboratory for help with the heat box, and M. Rosbash for the circadian software.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Wisconsin Madison, 6001 Research Park Blvd, Madison, Wisconsin, 53719, USA

    Chiara Cirelli, Daniel Bushey, Sean Hill, Reto Huber & Giulio Tononi

  2. Laboratory of Genetics, University of Wisconsin Madison, 445 Henry Mall, Madison, Wisconsin, 53706, USA

    Robert Kreber & Barry Ganetzky

Authors
  1. Chiara Cirelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Bushey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sean Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reto Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Kreber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Barry Ganetzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giulio Tononi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giulio Tononi.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure S1

Activity histograms in 3 representative mns female flies over two days in light-dark (LD 1-2) and two days in constant darkness (DD 5-6). (JPG 30 kb)

Supplementary Figure S2

Genetic mapping of the shaking and short sleeping phenotype in mns flies. (JPG 39 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cirelli, C., Bushey, D., Hill, S. et al. Reduced sleep in Drosophila Shaker mutants. Nature 434, 1087–1092 (2005). https://doi.org/10.1038/nature03486

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature03486

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing