Mechanisms of sleep induction by a sleep-active neuron

• Applicant: Professor Dr. Henrik Bringmann
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Animal Physiology and Biochemistry ; Sensory and Behavioural Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 450869693

Sleep is essential for animal life and is found from jellyfish to humans. Across species, sleep is an active state induced by sleep-active neurons that cause the shutdown of wakefulness circuits. However, little is known about the cellular and molecular mechanisms by which sleep-active neurons systemically control wake circuits. As sleep is highly conserved, it can be studied in molecularly accessible model organisms. In C. elegans, sleep is defined by behavioral criteria such as an increased arousal threshold, reversibility and homeostasis. Sleep induction in C. elegans crucially requires a single sleep-active neuron called RIS. This neuron promotes sleep through the release of neuropeptides encoded by the flp-11 gene. However, it is not known what neurons are controlled by RIS, and how their physiology is altered through neuropeptide receptors. In this proposal we will analyze how RIS controls the activity of downstream neurons. We will study both, neurons that are postsynaptic to RIS, as well as the global network of neurons that is controlled by RIS. We will characterize FLP-11 neuropeptide signaling and their effects on sleep induction by studying FLP-11 receptor mutants. Thus, we will delineate a circuit and molecular mechanism for sleep induction in a compact nervous system. This project will uncover the crucial nodes of the nervous system that need to be controlled for sleep induction and will show how neuropeptide receptors dampen wakefulness circuits. The results will serve as a roadmap to study sleep in other organisms including humans.

• DFG Programme: Research Grants