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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....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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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. |
format | Online Article Text |
id | pubmed-9407311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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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