Analysis of Touch Response & Habituation in C. elegans

描述(申请人提供)：学习涉及神经回路功能特性的长期变化，通过长期使用药物而不适当地激活这些可塑性机制被认为是药物耐受和依赖的基础。因此，了解单个神经元的功能变化是如何在神经回路的背景下改变行为的，这是成瘾研究中的一个关键挑战。 这项拟议的研究的目标是使用体内钙成像来研究线虫长期学习的一种简单形式--触摸习惯化的细胞基础。我们将通过可视化触摸神经元对机械刺激的反应来表征线虫机械感受器的正常反应和适应特性。此外，通过分析克隆的机械感觉基因对触觉细胞活性的影响，我们将确定这些神经元中机械转导的分子需求，并深入了解特定分子在机械转导中的作用。最后，通过同时成像机械感觉回路中多个神经元的活动，我们将获得关于触摸习惯性的细胞机制的信息。总之，这些实验将解决有关线虫机械感觉和神经可塑性的分子机制的关键悬而未决的问题，并可能为了解脊椎动物的类似过程提供洞察力。这些研究还将为改进光学成像方法提供一个试验场，这可能有助于将这一尖端技术应用于其他遗传易驯化的生物。

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.