State-Dependent Effects of Ethanol in C. elegans

描述(由申请者提供)：我们正在研究使用情景学习 以秀丽隐杆线虫嗅觉适应为模型。当蠕虫暴露在高潮中时 长时间浓缩诱人的气味，它们就会变成 在一种称为嗅觉适应的过程中对气味不敏感。我们有 发现乙醇对适应产生状态依赖：蠕虫暴露 同时对高浓度的气味和乙醇只能证明 如果在接触乙醇的情况下进行测试，它们对气味的适应性。如果 训练期结束后，蠕虫被从乙醇中移除，它们不再 展示对气味的适应。实际上，这些动物经历了 依赖国家的学习。我们还发现，这种学习需要正常的 多巴胺能功能。这个测试提供了一个研究的机会 使用分子遗传学方法的状态依赖学习。我们已经开始了 基因筛查以发现扰乱这一过程的突变，并已确定 一种扰乱依赖状态学习的突变。分子表征 这一突变和其他突变的研究将为深入了解 在线虫身上学习。我们还将使用药物操纵和 现有的突变体扰乱特定的神经化学途径以确定 这对这个学习很重要。

DESCRIPTION (provided by applicant): We are studying contextual learning using C. elegans olfactory adaptation as a model. When worms are exposed to a high concentration of an attractive odorant for a prolonged period, they become insensitive to the odorant in a process termed olfactory adaptation. We have found that ethanol generates a state-dependency to adaptation: Worms exposed simultaneously to a high concentration of odorant and ethanol only demonstrate adaptation to the odorant if they are tested while being exposed to ethanol. If the worms are removed from ethanol after the training period, they no longer display adaptation to the odorant. In effect, these animals have experienced state-dependent learning. We have also found that this learning requires normal dopaminergic function. This assay provides an opportunity to study state-dependent learning using a molecular genetics approach. We have begun genetic screens to find mutations that disrupt the process, and have identified one mutation that disrupts state-dependent learning. Molecular characterization of this and other mutations will provide insight into the mechanisms of learning in C. elegans. We will also use pharmacological manipulations and existing mutants to disrupt particular neurochemical pathways to determine which are important for this learning.