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

Pedro Machado Almeida, Blanca Lago Solis, Luca Stickley, Alexis Feidler and Emi Nagoshi ()
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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
Emi Nagoshi: Sciences III, University of Geneva

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26031-2

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