2. Academic Validation
  3. Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

  • Curr Biol. 2020 Jan 6;30(1):1-16.e13. doi: 10.1016/j.cub.2019.10.048.
Jan Konietzka 1,  Maximilian Fritz 2,  Silvan Spiri 3,  Rebecca McWhirter 4,  Andreas Leha 5,  Sierra Palumbos 4,  Wagner Steuer Costa 6,  Alexandra Oranth 6,  Alexander Gottschalk 6,  David M Miller 3rd 4,  Alex Hajnal 7,  Henrik Bringmann 8
Affiliations

Affiliations

  • 1 Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Department of Animal Physiology and Neurophysiology, Philipps University Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany.
  • 2 Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
  • 3 Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland; Molecular Life Science PhD Program, University of Zurich and ETH Zurich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
  • 4 Vanderbilt University, 3120 MRB III, Nashville, TN 37240-7935, USA.
  • 5 Georg August University Göttingen, Institute for Medical Statistics, Humboldtallee 32, 37073 Göttingen, Germany.
  • 6 Goethe University Frankfurt, Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Max-von-Laue-Str. 15, 60438 Frankfurt, Germany.
  • 7 Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
  • 8 Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany; Department of Animal Physiology and Neurophysiology, Philipps University Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany. Electronic address: henrik.bringmann@biologie.uni-marburg.de.
PMID: 31839447 DOI: 10.1016/j.cub.2019.10.048
Abstract

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.

Keywords

C. elegans; Caenorhabditis elegans; EGF; EGFR; calcium imaging; drowsiness; neural circuits; optogenetics; sleep.

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