Schlichting, M., Richhariya, S., Herndon, N., Ma, D., Xin, J., Lenh, W., Abruzzi, K., Rosbash, M. (2022). Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep.  Proc. Natl. Acad. Sci. U.S.A. 119(34): e2206066119.

FBrf0254216

Research paper

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single-cell sequencing indicates that they are not only enriched but also differentially expressed and contribute to clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy by introducing a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

PMC9407311 (PMC) (EuropePMC)