Molecular resolution of a behavioral paradox: sleep and arousal are regulated by distinct acetylcholine receptors in different neuronal types in Drosophila

Sleep and arousal are both important for animals. The neurotransmitter acetylcholine (ACh) has long been found to promote both sleep and arousal in mammals, an apparent paradox which has also been found to exist in flies, causing much confusion in understanding sleep and arousal. Here, we have systematically studied all 13 ACh receptors (AChRs) in Drosophila to understand mechanisms underlying ACh function in sleep and arousal. We found that exogenous stimuli-induced arousal was decreased in nAChR alpha 3 mutants, whereas sleep was decreased in nAChR alpha 2 and nAChR beta 2 mutants. nAChR alpha 3 functions in dopaminergic neurons to promote exogenous stimuli-induced arousal, whereas nAChR alpha 2 and beta 2 function in octopaminergic neurons to promote sleep. Our studies have revealed that a single transmitter can promote endogenous sleep and exogenous stimuli-induced arousal through distinct receptors in different types of downstream neurons.

Automated summary

Sleep and arousal are both crucial for animals, and the neurotransmitter acetylcholine plays an important role in regulating them. Research has shown that different types of ACh receptors in Drosophila control sleep and arousal through distinct mechanisms in different neurons.