Control of sleep-like behavior through a kinase and an ion channel subunit

• Applicant: Professor Dr. Henrik Bringmann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; General Genetics and Functional Genome Biology ; Sensory and Behavioural Biology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255318839

Sleep is a complex behavioral state that is found in mammals and that is essential for survival. But also all other animals that have been carefully studied, display quiescence behavior. Several of these quiescence behaviors fulfill behavioral criteria that define sleep in mammals such as an absence of voluntary movement, reversibility, increased arousal threshold, assumption of a specific posture, homeostatic regulation, and changes in the nervous system. It seems like these sleep-like states are much less complex compared with sleep in mammals but it may be that sleep and sleep-like states are evolutionarily related. Quiescent behavior can also be found in C. elegans. Little is known about the molecular control of sleep in any system. C. elegans allows the combination of behavioral analysis with functional neural imaging and genetics, and thus is valuable system to study the molecular basis of sleep-like behavior. To understand the molecular and neural mechanisms underlying sleep-like behavior in C. elegans by lab has performed genetic screening for mutants that are defective in quiescence behavior. Reverse genetic screening identified two genes that are important to control sleep-like behavior that I would like to study in this proposal. One of these genes encodes a putative kinase, and the other encodes a calcium channel subunit. The aim of this proposal is to understand how a kinase and calcium channel subunit control sleep-like behavior. The aim of this proposal is to understand how the putative kinase and the ion channel subunit gene control sleep-like behavior. I want to answer the following questions: What neurons show defective activity during sleep-like behavior the mutants? Is responsiveness to stimulation reduced during sleep-like behavior the mutants? In which cells is the mutated gene expressed and does its expression change with the sleep-wake-like cycle? What are the cells in which the genes that are mutated need to be expressed to control sleep-like behavior? What is the role of the activity of the neurons that require expression of the genes mutated in sleep control? Is the putative kinase actually a kinase? Is the putative cyclin-dependent kinase cyclin dependent? Does the ion channel subunit control the excitability of neurons to achieve sleep-like behavior? Is the expression or trafficking of the channel complex regulated during sleep-like behavior? Answering these questions will lead to circuit and molecular insight into how sleep-like behavior is regulated.

• DFG Programme: Research Grants