Optogenetic activation of SIFamide (SIFa) neurons induces a complex sleep-promoting effect in the fruit fly Drosophila melanogaster.

Sleep is a universal and extremely complicated function. Sleep is regulated by two systems-sleep homeostasis and circadian rhythms. In a wide range of species, neuropeptides have been found to play a crucial role in the communication and synchronization between different components of both systems. In the fruit fly Drosophila melanogaster, SIFamide (SIFa) is a neuropeptide that has been reported to be expressed in 4 neurons in the pars intercerebralis (PI) area of the brain. Previous work has shown that transgenic ablation of SIFa neurons, mutation of SIFa itself, or knockdown of SIFa receptors reduces sleep, suggesting that SIFa is sleep-promoting. However, those were all constitutive manipulations that could have affected development or resulted in compensation, so the role of SIFa signaling in sleep regulation during adulthood remains unclear. In the current study, we examined the sleep-promoting effect of SIFa through an optogenetic approach, which allowed for neuronal activation with high temporal resolution, while leaving development unaffected. We found that activation of the red-light sensor Chrimson in SIFa neurons promoted sleep in flies in a sexually dimorphic manner, where the magnitude of the sleep effect was greater in females than in males. Because neuropeptidergic neurons often also release other transmitters, we used RNA interference to knock down SIFa while also optogenetically activating SIFa neurons. SIFa knockdown only partially reduced the magnitude of the sleep effect, suggesting that release of other transmitters may contribute to the sleep induction when SIFa neurons are activated. Video-based analysis showed that activation of SIFa neurons for as brief a period as 1 second was able to decrease walking behavior for minutes after the stimulus. Future studies should aim to identify the transmitters that are utilized by SIFa neurons and characterize their upstream activators and downstream targets. It would also be of interest to determine how acute optogenetic activation of SIFa neurons alters other behaviors that have been linked to SIFa, such as mating and feeding.