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Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

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....

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Autores principales: Schlichting, Matthias, Richhariya, Shlesha, Herndon, Nicholas, Ma, Dingbang, Xin, Jason, Lenh, William, Abruzzi, Katharine, Rosbash, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407311/
https://www.ncbi.nlm.nih.gov/pubmed/35969763
http://dx.doi.org/10.1073/pnas.2206066119
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author Schlichting, Matthias
Richhariya, Shlesha
Herndon, Nicholas
Ma, Dingbang
Xin, Jason
Lenh, William
Abruzzi, Katharine
Rosbash, Michael
author_facet Schlichting, Matthias
Richhariya, Shlesha
Herndon, Nicholas
Ma, Dingbang
Xin, Jason
Lenh, William
Abruzzi, Katharine
Rosbash, Michael
author_sort Schlichting, Matthias
collection PubMed
description 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.
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spelling pubmed-94073112022-08-26 Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep Schlichting, Matthias Richhariya, Shlesha Herndon, Nicholas Ma, Dingbang Xin, Jason Lenh, William Abruzzi, Katharine Rosbash, Michael Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2022-08-15 2022-08-23 /pmc/articles/PMC9407311/ /pubmed/35969763 http://dx.doi.org/10.1073/pnas.2206066119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Schlichting, Matthias
Richhariya, Shlesha
Herndon, Nicholas
Ma, Dingbang
Xin, Jason
Lenh, William
Abruzzi, Katharine
Rosbash, Michael
Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title_full Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title_fullStr Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title_full_unstemmed Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title_short Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep
title_sort dopamine and gpcr-mediated modulation of dn1 clock neurons gates the circadian timing of sleep
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9407311/
https://www.ncbi.nlm.nih.gov/pubmed/35969763
http://dx.doi.org/10.1073/pnas.2206066119
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