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A dynamic role for the mushroom bodies in promoting sleep in Drosophila

Naturevolume 441pages753756 (2006) | Download Citation

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Abstract

The fruitfly, Drosophila melanogaster, exhibits many of the cardinal features of sleep, yet little is known about the neural circuits governing its sleep1. Here we have performed a screen of GAL4 lines expressing a temperature-sensitive synaptic blocker shibirets1 (ref. 2) in a range of discrete neural circuits, and assayed the amount of sleep at different temperatures. We identified three short-sleep lines at the restrictive temperature with shared expression in the mushroom bodies, a neural locus central to learning and memory3. Chemical ablation of the mushroom bodies also resulted in reduced sleep. These studies highlight a central role for the mushroom bodies in sleep regulation.

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References

  1. 1

    Hendricks, J. C. & Sehgal, A. Why a fly? Using Drosophila to understand the genetics of circadian rhythms and sleep. Sleep 27, 334–342 (2004)

  2. 2

    Kitamoto, T. Conditional modification of behaviour in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J. Neurobiol. 47, 81–92 (2001)

  3. 3

    Davis, R. L. Olfactory learning. Neuron 44, 31–48 (2004)

  4. 4

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

  5. 5

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

  6. 6

    Hendricks, J. C., Kirk, D., Panckeri, K., Miller, M. S. & Pack, A. I. Modafinil maintains waking in the fruit fly Drosophila melanogaster. Sleep 26, 139–146 (2003)

  7. 7

    van Swinderen, B., Nitz, D. A. & Greenspan, R. J. Uncoupling of brain activity from movement defines arousal states in Drosophila. Curr. Biol. 14, 81–87 (2004)

  8. 8

    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)

  9. 9

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

  10. 10

    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)

  11. 11

    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)

  12. 12

    Cirelli, C. et al. Reduced sleep in Drosophila Shaker mutants. Nature 434, 1087–1092 (2005)

  13. 13

    Kosaka, T. & Ikeda, K. Possible temperature-dependent blockage of synaptic vesicle recycling induced by a single gene mutation in Drosophila. J. Neurobiol. 14, 207–225 (1983)

  14. 14

    van der Bliek, A. M. & Meyerowitz, E. M. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 351, 411–414 (1991)

  15. 15

    Chen, M. S. et al. Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis. Nature 351, 583–586 (1991)

  16. 16

    Koenig, J. H., Saito, K. & Ikeda, K. Reversible control of synaptic transmission in a single gene mutant of Drosophila melanogaster. J. Cell Biol. 96, 1517–1522 (1983)

  17. 17

    Armstrong, J. D. & Kaiser, K. Flytrap lines. www.fly-trap.org (1996).

  18. 18

    Pascual, A. & Preat, T. Localization of long-term memory within the Drosophila mushroom body. Science 294, 1115–1117 (2001)

  19. 19

    Zars, T., Fischer, M., Schulz, R. & Heisenberg, M. Localization of a short-term memory in Drosophila. Science 288, 672–675 (2000)

  20. 20

    Martin, J. R., Ernst, R. & Heisenberg, M. Mushroom bodies suppress locomotor activity in Drosophila melanogaster. Learn. Mem. 5, 179–191 (1998)

  21. 21

    Schwaerzel, M., Heisenberg, M. & Zars, T. Extinction antagonizes olfactory memory at the subcellular level. Neuron 35, 951–960 (2002)

  22. 22

    Sapp, R. J., Christianson, J. & Stark, W. S. Turnover of membrane and opsin in visual receptors of normal and mutant Drosophila. J. Neurocytol. 20, 597–608 (1991)

  23. 23

    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)

  24. 24

    de Belle, J. S. & Heisenberg, M. Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. Science 263, 692–695 (1994)

  25. 25

    Helfrich-Forster, C., Wulf, J. & de Belle, J. S. Mushroom body influence on locomotor activity and circadian rhythms in Drosophila melanogaster. J. Neurogenet. 16, 73–109 (2002)

  26. 26

    Li, W., Ohlmeyer, J. T., Lane, M. E. & Kalderon, D. Function of protein kinase A in hedgehog signal transduction and Drosophila imaginal disc development. Cell 80, 553–562 (1995)

  27. 27

    Belgacem, Y. H. & Martin, J. R. Neuroendocrine control of a sexually dimorphic behaviour by a few neurons of the pars intercerebralis in Drosophila. Proc. Natl. Acad. Sci. USA 99, 15154–15158 (2002)

  28. 28

    Siegmund, T. & Korge, G. Innervation of the ring gland of Drosophila melanogaster. J. Comp. Neurol. 431, 481–491 (2001)

  29. 29

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

  30. 30

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

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Acknowledgements

We thank M. Villar, A. Schroeder, B. Finn, D. Hanrahan, A. Majeed and A. Phillips for assistance with PCR genotyping (M.V.), confocal imaging (A.S., B.F.), initial screening (D.H., A.M.) and designing data analysis software (A.P.); C. Cirelli and G. Tononi and their laboratories for advice on mechanical sleep deprivation; P. Shaw, T. Zars, M. Rosbash and E. Smith for comments; and B. Joiner and A. Sehgal for communicating results before publication. This work was supported by a Burroughs Wellcome Career Award in the Biomedical Sciences and by the NIH (R.A.). Author Contributions J.L.P. completed all experiments and analyses, with assistance on lifespan, PCR genotyping and general fly maintenance from J.J.McG., and on the development and application of behaviour data analysis software for measures of sleep intensity (the Drosophila Activity Monitor Data Crunching Macro) from K.P.K. J.L.P. and R.A. wrote the manuscript.

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  1. Department of Neurobiology and Physiology, Northwestern University, Evanston, Ilinois, 60208, USA

    • Jena L. Pitman
    • , Jermaine J. McGill
    • , Kevin P. Keegan
    •  & Ravi Allada

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Correspondence to Ravi Allada.

Supplementary information

  1. Supplementary Notes

    This file contains the Supplementary Methods, Supplementary Table 1 and Supplementary Figures 1–5. (PDF 1356 kb)

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https://doi.org/10.1038/nature04739

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