eNeuro · 2018 · 46 citations · 59 references
Life SciencesNeurobiologyNeuroscienceCircadian RhythmsMolecular NeuroscienceSignal TransductionCircadian Clock MechanismsCircadian Molecular MechanismsCircadian PhysiologyDopaminergic SignalingSleep-wake NeurobiologySleep-wake RegulationCircadian Regulation Of SleepDopaminergic NeuronsDrosophila ModelsNeuronal Control Of WakefulnessSleep-wake CircuitrySleep-wake Cycle RegulationWake RegulationWakefulness Promotion
Circadian clocks modulate timing of sleep/wake cycles in animals; however, the underlying mechanisms remain poorly understood. In Drosophila melanogaster , large ventral lateral neurons (l-LN v ) are known to promote wakefulness through the action of the neuropeptide pigment dispersing factor (PDF), but the downstream targets of PDF signalling remain elusive. In a screen using downregulation or overexpression (OEX) of the gene encoding PDF receptor ( pdfr ), we found that a subset of dopaminergic neurons responds to PDF to promote wakefulness during the day. Moreover, we found that small LN v (s-LN v ) and dopaminergic neurons form synaptic contacts, and PDFR signalling inhibited dopaminergic neurons specifically during day time. We propose that these dopaminergic neurons that respond to PDFR signalling are sleep-promoting and that during the day when PDF levels are high, they are inhibited, thereby promoting wakefulness. Thus, we identify a novel circadian clock pathway that mediates wake promotion specifically during day time.
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