Analysis of Touch Response & Habituation in C. elegans

描述（由申请人提供）：学习涉及神经回路功能特性的长期变化，通过长期使用药物对这些可塑性机制的不适当激活被认为是药物耐受性和依赖性的基础。因此，了解单个神经元的功能变化如何在神经回路的背景下改变行为，是成瘾研究中的一个关键挑战。 这项研究的目的是利用体内钙离子成像技术来研究线虫C.优雅我们将描述C.通过可视化触觉神经元对机械刺激的反应来研究秀丽隐杆线虫机械感受器。此外，通过分析克隆的mechanosensory基因对触觉细胞活性的影响，我们将定义这些神经元中mechanosensory转导的分子要求，并深入了解特定分子在mechanosensory转导中的作用。最后，通过同时成像机械感觉回路中多个神经元的活动，我们将获得有关触摸习惯化的细胞机制的信息。总之，这些实验将解决关键的悬而未决的问题，关于机械感觉和神经可塑性的分子机制，在C。elegans，并有可能提供洞察类似的过程在脊椎动物。这些研究还将为光学成像方法的改进提供一个试验场，这可能有助于将这一尖端技术应用于其他遗传上易于处理的生物。

DESCRIPTION (provided by applicant): Learning involves long-lasting changes in the functional properties of neural circuits, and inappropriate activation of these plasticity mechanisms through chronic drug use is thought to underlie drug tolerance and dependence. Understanding how functional changes in individual neurons act within the context of a neural circuit to modify behavior therefore represents a critical challenge in the study of addiction. The goal of the proposed research is to use in vivo calcium imaging to investigate the cellular basis of a simple form of long-term learning, touch habituation, in the nematode C. elegans. We will characterize the normal response and adaptation properties of C. elegans mechanoreceptors by visualizing the activity of touch neurons in response to mechanical stimulation. In addition, by assaying the effect of cloned mechanosensory genes on touch cell activity we will define the molecular requirements for mechanotransduction in these neurons and gain insight into the roles of specific molecules in mechanotransduction. Finally, by simultaneously imaging the activity of multiple neurons in the mechanosensory circuitry, we will gain information about the cellular mechanisms underlying touch habituation. Together, these experiments will address key unanswered questions regarding the molecular mechanisms of mechanosensation and neural plasticity in C. elegans, and are likely to provide insight into analogous processes in vertebrates. These studies will also provide a proving ground for improvements in optical imaging methodologies, which could facilitate the application of this cutting-edge technology to other genetically tractable organisms.