Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
Abstract 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 differentially expressed but also define clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy with a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.
Abruzzi K.、Schlichting M.、Herndon N.、Ma D.、Richhariya S.、Lenh W.、Rosbash M.、Xin J.
Howard Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis University||Northeastern University, College of Science, Department of BiologyHoward Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis UniversityHoward Hughes Medical Institute, Department of Biology, Brandeis University
基础医学生理学分子生物学
Abruzzi K.,Schlichting M.,Herndon N.,Ma D.,Richhariya S.,Lenh W.,Rosbash M.,Xin J..Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2021.12.16.472997.点此复制
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