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Sleep in Drosophila is regulated by adult mushroom bodies


Sleep is one of the few major whole-organ phenomena for which no function and no underlying mechanism have been conclusively demonstrated. Sleep could result from global changes in the brain during wakefulness or it could be regulated by specific loci that recruit the rest of the brain into the electrical and metabolic states characteristic of sleep. Here we address this issue by exploiting the genetic tractability of the fruitfly, Drosophila melanogaster, which exhibits the hallmarks of vertebrate sleep1,2,3,4. We show that large changes in sleep are achieved by spatial and temporal enhancement of cyclic-AMP-dependent protein kinase (PKA) activity specifically in the adult mushroom bodies of Drosophila. Other manipulations of the mushroom bodies, such as electrical silencing, increasing excitation or ablation, also alter sleep. These results link sleep regulation to an anatomical locus known to be involved in learning and memory.

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Figure 1: Expression of PKA in various regions of the fly brain affects sleep differentially.
Figure 2: Localization of GAL4-dependent brain expression.
Figure 3: Inducible expression of PKA in the MBs leads to decreased sleep bout duration and accumulation of sleep debt.
Figure 4: Decreasing and increasing excitability in a subset of MB neurons have opposite effects on sleep.


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We thank G. Roman and R. Davis for P{MB-Switch}, and L. Griffith, T. Kitamoto, R. Greenspan, J. D. Armstrong, K. Kaiser, R. Allada and C. Hellfrich-Forster for other GAL4 lines; J. Hendricks for advice on studying fly sleep; E. Friedman, S. Harbison, K. Ho, K. Koh, S. Sathyanarayanan, M. Wu, Q. Yuan and X. Zheng for critical comments on the manuscript; and K. Liu for assistance with animal maintenance. We also thank J. Pitman and R. Allada for communicating results before publication. W.J.J. and A.C. were supported by training grants to the Center for Sleep and Respiratory Neurobiology at the University of Pennsylvania, and W.J.J. was also supported by a Pickwick Fellowship from the National Sleep Foundation. Partial support was provided by a programme project grant from the NIA. B.H.W. was supported by the Intramural Research Program of the NIH, NIMH. Author Contributions W.J.J. conducted the behavioural experiments, wrote the sleep analysis software, analysed the sleep data, prepared fly brains and heads for confocal microscopy and PKA assays, and co-wrote the manuscript. A.C. assisted with the behavioural experiments and sleep analysis, prepared fly brains for imaging, performed all confocal microscopy, and provided feedback on the manuscript. B.H.W. provided NaChBac transgenic animals and feedback on the manuscript. A.S. conceived the project, provided guidance and critical interpretation during the project, co-wrote the manuscript and provided financial support.

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Correspondence to Amita Sehgal.

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Supplementary information

Supplementary Table 1

Listing of the major expression pattern in the brain of all GAL4 drivers used in the study. (DOC 36 kb)

Supplementary Figure 1

Expression of different GAL4 drivers in the peduncles of MBs. (PDF 922 kb)

Supplementary Figure 2

Behavioral and expression data for two MB drivers that have sleep-promoting and sleep-inhibiting effects when they drive expression of PKA. (PDF 1060 kb)

Supplementary Figure 3

Supplementary Figure 3 nature04811-s4.pdf Sleep architecture of flies expressing PKA under the control of a sleep-inhibiting and a sleep-promoting driver respectively. (PDF 552 kb)

Supplementary Figure 4

Homeostatic rebound produced by 12 hours of mechanical sleep deprivation in uninduced MB-Switch/PKA flies. (PDF 611 kb)

Supplementary Figure 5

Effect on sleep of expressing the EKO potassium channel in MB-Switch neurons. (PDF 455 kb)

Supplementary Figure 6

Effect of ablating MBs on sleep and activity. (PDF 472 kb)

Supplementary Figure 7

Model for the regulation of sleep by MBs (PDF 446 kb)

Supplementary Figure Legends

Legends are provided for all the figures listed above. (DOC 28 kb)

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Joiner, W., Crocker, A., White, B. et al. Sleep in Drosophila is regulated by adult mushroom bodies. Nature 441, 757–760 (2006).

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