Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
Matthias Schlichting, Shlesha Richhariya, Nicholas Herndon, Dingbang Ma, Jason Xin, William Lenh, Katharine C. Abruzzi, Michael Rosbash
Abstract
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.