No abstract

Sleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wakeactive 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 interneuronswhich 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.

She works in the group of Prof. Bringmann with a focus on sleep in C. elegans. She received a Bachelor degree in physics from Princeton University, USA, in 2016. After that she started her PhD work in Prof. Bringmann's lab at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. The lab moved to Marburg, Germany, in May 2019, where she since then conducts her research and finishes her PhD projects. Florian Jordan works as an electronics technician for the electronics service at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. He finished his occasional training there in 2014 and since then he develops and repairs electrical equipment for research groups. In 2016 he received the CID certification, following this he started to study to become a statecertified technician.