The molecular and physiological basis of thermosensory behavior in C. elegans

描述（由申请人提供）：生物体利用各种感官来判断其环境的性质。这些外部线索影响内部通路，导致行为输出和发展的改变。本应用程序旨在从基因到行为输出对秀丽隐杆线虫的热感觉行为进行阐明，以便更好地了解热感觉信号转导和可塑性的机制。秀丽隐杆线虫感知温度并产生对温度的“记忆”，这反过来又决定了它们在空间或时间温度梯度上的导航行为策略。这种热存储器是塑料的，可以在暴露于新的温度时重置。为了更好地理解这种感觉形态和感觉可塑性，新开发的定量行为分析将用于确定候选分子的贡献，从而概述负责热感觉行为的潜在遗传和生化途径。钙成像也将用于确定这些候选分子在分子途径中的作用。最后，将观察候选蛋白的亚细胞定位，以响应不同的温度刺激，以更好地了解蛋白质在细胞中的作用，以介导适当的行为。这些方法的结合将提供第一个涉及热感觉和塑性定义方面的保守分子的综合分析。多种疾病如视网膜变性和无法感知疼痛是由感觉信号通路缺陷引起的。虽然我们对脊椎动物和无脊椎动物的视觉和化学感觉信号转导了解很多，但热感觉的特征仍然很差。研究秀丽隐杆线虫的热感觉，将有助于确定在多种生物中可能保守的感觉信号转导分子的功能。秀丽隐杆线虫在其热感觉反应中也表现出长期的可塑性。神经可塑性的不规则性与许多人类疾病有关，包括药物成瘾、神经元变性和癫痫。通过秀丽隐杆线虫的热感觉行为来研究神经元的可塑性，将揭示高级生物神经系统中涉及的保守分子和机制。

DESCRIPTION (provided by applicant): Organisms utilize a variety of senses to judge the nature of their environment. These external cues influence internal pathways resulting in altered behavioral output and development. This application aims to elucidate thermosensory behaviors of C. elegans from gene to behavioral output, in order to better understand mechanisms of sensory signal transduction and plasticity. C. elegans senses temperature and creates a 'memory' of this temperature, which in turn dictates the navigation behavioral strategy on spatial or temporal thermal gradients. This thermal memory is plastic and can be reset upon exposure to a new temperature. In order to better understand this sensory modality and sensory plasticity in general, newly developed quantitative behavioral assays will be utilized to identify the contribution of candidate molecules, thereby outlining the underlying genetic and biochemical pathways responsible for thermosensory behavior. Calcium imaging will also be utilized in order to define where in the molecular pathway these candidate molecules function. Finally, subcellular localization of the candidate proteins will be observed in response to different temperature stimuli to gain a better understanding of where in the cell the protein acts to mediate the appropriate behavior. The combination of these approaches will provide the first comprehensive analysis of conserved molecules involved in defined aspects of thermosensation and plasticity. Multiple disorders such as retinal degeneration and inability to sense pain result from defects in sensory signaling pathways. While much is known about visual and chemosensory signal transduction in vertebrates and invertebrates, thermosensation remains poorly characterized. Exploring thermosensation in C. elegans will identify the functions of sensory molecules likely conserved in sensory signal transduction in multiple organisms. C. elegans also demonstrates long-term plasticity in its thermosensory response. Irregularities in neuronal plasticity have been linked to a number of human disorders, including drug addiction, neuronal degeneration, and epilepsy. Studying neuronal plasticity via the thermosensory behavior of C. elegans will reveal conserved molecules and mechanisms involved in nervous systems of higher order organisms.