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Neurofibromin 1 in mushroom body neurons mediates circadian wake drive through activating cAMP–PKA signaling

Author

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  • Pedro Machado Almeida

    (Sciences III, University of Geneva)

  • Blanca Lago Solis

    (Sciences III, University of Geneva)

  • Luca Stickley

    (Sciences III, University of Geneva)

  • Alexis Feidler

    (Sciences III, University of Geneva
    University of Rochester School of Medicine and Dentistry)

  • Emi Nagoshi

    (Sciences III, University of Geneva)

Abstract

Various behavioral and cognitive states exhibit circadian variations in animals across phyla including Drosophila melanogaster, in which only ~0.1% of the brain’s neurons contain circadian clocks. Clock neurons transmit the timing information to a plethora of non-clock neurons via poorly understood mechanisms. Here, we address the molecular underpinning of this phenomenon by profiling circadian gene expression in non-clock neurons that constitute the mushroom body, the center of associative learning and sleep regulation. We show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons, including the Neurofibromin 1 (Nf1) tumor suppressor gene and Pka-C1. Circadian clocks also drive calcium rhythms in mushroom body neurons via NF1-cAMP/PKA-C1 signaling, eliciting higher mushroom body activity during the day than at night, thereby promoting daytime wakefulness. These findings reveal the pervasive, non-cell-autonomous circadian regulation of gene expression in the brain and its role in sleep.

Suggested Citation

  • Pedro Machado Almeida & Blanca Lago Solis & Luca Stickley & Alexis Feidler & Emi Nagoshi, 2021. "Neurofibromin 1 in mushroom body neurons mediates circadian wake drive through activating cAMP–PKA signaling," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26031-2
    DOI: 10.1038/s41467-021-26031-2
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    Cited by:

    1. Michaëla Majcin Dorcikova & Lou C. Duret & Emma Pottié & Emi Nagoshi, 2023. "Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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