A K+ Channel Learning Susceptibility Gene

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"This award is funded under the American Recovery and Reinvestment Act of 2009(Public Law 111-5)."Habituation is a form of non-associative learning in which repetition of a stimulus induces a progressive diminution of the behavioral response. The learning underlying habituation is a fundamental process of biological systems that is conserved from protozoans to humans. While habituation is well characterized at behavioral level, the molecular mechanisms which induce this form of learning have not been fully defined. In particular, it is not well understood how potassium channels, which are key players in controlling cellular excitability, contribute to this fundamental behavior. These studies are aimed at understanding the cellular and molecular mechanisms that induce habituation to mechanical stimulation, in the metazoan Caenorhabditis elegans. The principal investigator's laboratory discovered a novel gene, MPS-1, which is an accessory subunit of voltage-gated potassium channels and which possesses kinase activity. They have preliminary data that show that 1) MPS-1 forms a complex with voltage-gated K+ channel KHT-1 in the touch-sensing neurons of C. elegans and 2) that the kinase activity of MPS-1 specifically controls habituation in C. elegans through phosphorylation of KHT-1. In this project they propose to use a combination of genetic, electrophysiological measurements in dissected C. elegans neurons, confocal microscopy, optical measurements of calcium transients and animal model (i.e. mps-1 knock out worms, expression of MPS-1 variants in mps-1 knock outs etc.) studies to resolve the role of potassium currents in determining habituation to tap in C. elegans. This project might significantly advance our understanding of electrical mechanisms underlying habituation behavior because: 1) a new mechanism of K+ channel regulation will be elucidated; 2) habituation is an universal behavior exhibited by virtually all biological organisms including protozoans. Most importantly, trainees in the laboratory will receive first-rate guidance in a wide range of techniques, including but not limited to electrophysiology, genetics, biochemistry, microscopy and will be consequently very successful. In summary, the proposed research continues the commitment of the PI to provide training to all levels of students in the theory and practice of scientific research.