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A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis

Nature Neuroscience volume 4, pages 1108–1115 (2001)Cite this article

Abstract

In the fruit fly, Drosophila melanogaster, rest shares features with mammalian sleep, including prolonged immobility, decreased sensory responsiveness and a homeostatic rebound after deprivation. To understand the molecular regulation of sleep-like rest, we investigated the involvement of a candidate gene, cAMP response-element binding protein (CREB). The duration of rest was inversely related to cAMP signaling and CREB activity. Acutely blocking CREB activity in transgenic flies did not affect the clock, but increased rest rebound. CREB mutants also had a prolonged and increased homeostatic rebound. In wild types, in vivo CREB activity increased after rest deprivation and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasis in Drosophila.

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Figure 1: Changes in cAMP signaling and CREB activity altered rest duration and not locomotion.
Figure 2: Increased and prolonged rest rebound responses after rest deprivation in flies with blocked CREB activity.
Figure 3: The change in rest is not effected through the clock.
Figure 4: Prolonged and increased rest rebound in flies with a mutation in the dCREB2 gene (S162).
Figure 5: CRE-dependent gene expression increased during and after rest deprivation.

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Acknowledgements

This work was supported by grants (R01-HL-59649, SCOR-HL-60287) from the National Institutes of Heart, Lung and Blood (J.C.H., J.C.-P.Y.) and the Howard Hughes Medical Institute (A.S.). We thank J. Cater for biostatistical assistance and A.I. Pack for advice and support.

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Authors and Affiliations

  1. Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 991 Maloney Building, 3600 Spruce St, Philadelphia, 19104, Pennsylvania, USA

    Joan C. Hendricks, Julie A. Williams, Karen Panckeri, David Kirk & Amita Sehgal

  2. Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, 11724, New York, USA

    Marcela Tello & Jerry C.-P. Yin

  3. Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Amita Sehgal

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  1. Joan C. Hendricks
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Correspondence to Jerry C.-P. Yin.

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Hendricks, J., Williams, J., Panckeri, K. et al. A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nat Neurosci 4, 1108–1115 (2001). https://doi.org/10.1038/nn743

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