A K+ Channel Learning Susceptibility Gene

“这项奖励是根据2009年美国复苏和再投资法案（公法111-5）资助的。”习惯化是一种非联想学习的形式，在这种学习中，重复刺激会导致行为反应的逐渐减少。习惯化背后的学习是生物系统的一个基本过程，从原生动物到人类都是如此。虽然习惯化在行为水平上有很好的特征，但诱导这种学习形式的分子机制尚未完全确定。特别是，钾通道是控制细胞兴奋性的关键角色，它是如何促成这种基本行为的尚不清楚。这些研究旨在了解在后生动物秀丽隐杆线虫中诱导对机械刺激习惯化的细胞和分子机制。首席研究员的实验室发现了一种新的基因MPS-1，它是电压门控钾通道的附属亚基，具有激酶活性。他们有初步的数据表明，1)MPS-1在秀丽隐杆线虫的触摸感应神经元中与电压门控K+通道KHT-1形成复合物，2)MPS-1的激酶活性通过KHT-1的磷酸化特异性地控制秀丽隐杆线虫的习惯化。在这个项目中，他们建议结合遗传学，解剖秀丽隐杆线虫神经元的电生理测量，共聚焦显微镜，钙瞬态的光学测量和动物模型（即mps-1敲除蠕虫，mps-1变体在mps-1敲除中的表达等）研究来解决钾电流在决定秀丽隐杆线虫习惯化中的作用。该项目可能会显著促进我们对习惯行为背后的电学机制的理解，因为：1)将阐明K+通道调节的新机制；习惯化是包括原生动物在内的几乎所有生物都表现出的一种普遍行为。最重要的是，实验室的受训者将在广泛的技术方面获得一流的指导，包括但不限于电生理学，遗传学，生物化学，显微镜，因此将非常成功。总之，拟议的研究继续了PI的承诺，为各级学生提供科学研究理论和实践方面的培训。

"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.