Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit
| Autor: | Alexandra Oranth, Jan Konietzka, Henrik Bringmann, Alexander Gottschalk, Alex Hajnal, Silvan Spiri, Wagner Steuer Costa, Rebecca McWhirter, Sierra Palumbos, David M. Miller, Maximilian Fritz, Andreas Leha |
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| Přispěvatelé: | University of Zurich, Bringmann, Henrik |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
1100 General Agricultural and Biological Sciences Biology Optogenetics General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Calcium imaging 1300 General Biochemistry Genetics and Molecular Biology Epidermal growth factor medicine Biological neural network Animals Epidermal growth factor receptor Caenorhabditis elegans Caenorhabditis elegans Proteins Neurons Epidermal Growth Factor Depolarization 10124 Institute of Molecular Life Sciences 030104 developmental biology medicine.anatomical_structure biology.protein 570 Life sciences biology Neuron Signal transduction General Agricultural and Biological Sciences Sleep Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Current Biology |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2019.10.048 |
| Popis: | Summary Sleep requires sleep-active neurons that depolarize to inhibit wake circuits. Sleep-active neurons are under the control of homeostatic mechanisms that determine sleep need. However, little is known about the molecular and circuit mechanisms that translate sleep need into the depolarization of sleep-active neurons. During many stages and conditions in C. elegans, sleep requires a sleep-active neuron called RIS. Here, we defined the transcriptome of RIS and discovered that genes of the epidermal growth factor receptor (EGFR) signaling pathway are expressed in RIS. Because of cellular stress, EGFR directly activates RIS. Activation of EGFR signaling in the ALA neuron has previously been suggested to promote sleep independently of RIS. Unexpectedly, we found that ALA activation promotes RIS depolarization. Our results suggest that ALA is a drowsiness neuron with two separable functions: (1) it inhibits specific behaviors, such as feeding, independently of RIS, (2) and it activates RIS. Whereas ALA plays a strong role in surviving cellular stress, surprisingly, RIS does not. In summary, EGFR signaling can depolarize RIS by an indirect mechanism through activation of the ALA neuron that acts upstream of the sleep-active RIS neuron and through a direct mechanism using EGFR signaling in RIS. ALA-dependent drowsiness, rather than RIS-dependent sleep bouts, appears to be important for increasing survival after cellular stress, suggesting that different types of behavioral inhibition play different roles in restoring health. Video Abstract Download : Download video (45MB) |
| Databáze: | OpenAIRE |
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