A wake-active locomotion circuit depolarizes a sleep-active neuron to switch on sleep

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Elisabeth Maluck - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Inka Busack - , Chair of Cellular Circuits and Systems, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), University Hospital Gießen and Marburg (Author)
  • Judith Besseling - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Florentin Masurat - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Michal Turek - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Karl Emanuel Busch - , Edinburgh Napier University (Author)
  • Henrik Bringmann - , Chair of Cellular Circuits and Systems, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), University Hospital Gießen and Marburg (Author)

Abstract

Sleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wake-active wake-promoting neurons in turn shut down sleep-active neurons, thus forming a bipartite flip-flop switch. However, how sleep is switched on is unclear because it is not known how wakefulness is translated into sleep-active neuron depolarization when the system is set to sleep. Using optogenetics in Caenorhabditis elegans, we solved the presynaptic circuit for depolarization of the sleep-active RIS neuron during developmentally regulated sleep, also known as lethargus. Surprisingly, we found that RIS activation requires neurons that have known roles in wakefulness and locomotion behavior. The RIM interneurons-which are active during and can induce reverse locomotion-play a complex role and can act as inhibitors of RIS when they are strongly depolarized and as activators of RIS when they are modestly depolarized. The PVC command interneurons, which are known to promote forward locomotion during wakefulness, act as major activators of RIS. The properties of these locomotion neurons are modulated during lethargus. The RIMs become less excitable. The PVCs become resistant to inhibition and have an increased capacity to activate RIS. Separate activation of neither the PVCs nor the RIMs appears to be sufficient for sleep induction; instead, our data suggest that they act in concert to activate RIS. Forward and reverse circuit activity is normally mutually exclusive. Our data suggest that RIS may be activated at the transition between forward and reverse locomotion states, perhaps when both forward (PVC) and reverse (including RIM) circuit activity overlap. While RIS is not strongly activated outside of lethargus, altered activity of the locomotion interneurons during lethargus favors strong RIS activation and thus sleep. The control of sleep-active neurons by locomotion circuits suggests that sleep control may have evolved from locomotion control. The flip-flop sleep switch in C. elegans thus requires an additional component, wake-active sleep-promoting neurons that translate wakefulness into the depolarization of a sleep-active neuron when the worm is sleepy. Wake-active sleep-promoting circuits may also be required for sleep state switching in other animals, including in mammals.

Details

Original languageEnglish
Article numbere3000361
JournalPLoS biology
Volume18
Issue number2
Publication statusPublished - Feb 2020
Peer-reviewedYes

External IDs

PubMedCentral PMC7053779
Scopus 85081122023
ORCID /0000-0001-8410-0006/work/141543469
ORCID /0000-0002-7689-8617/work/142236967

Keywords

Keywords

  • Animals, Arousal/physiology, Behavior, Animal/physiology, Caenorhabditis elegans/physiology, Caenorhabditis elegans Proteins/genetics, Calcium/metabolism, Homeostasis, Interneurons/metabolism, Larva/physiology, Locomotion/physiology, Neural Pathways/physiology, Neurons/metabolism, Optogenetics, Sleep Stages/physiology, Wakefulness/physiology

Library keywords