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

线虫热感行为的分子和生理学基础

• 批准号: 7618757
• 负责人: Sara M Wasserman
• 金额: $ 2.63万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618757
• 关键词: Behavior; Behavioral; Behavioral Assay; Biochemical Pathway; Biological Assay; Caenorhabditis elegans; Calcium; Candidate Disease Gene; Cells; Complex; Cues; Defect; Development; Disease; Drug Addiction; Environment; Epilepsy; Exposure to; Genes; Genetic; Goals; Human; Image; Interneurons; Invertebrates; Link; Measurement; Mediating; Memory; Modality; Molecular; Nature; Nerve Degeneration; Nervous system structure; Neuronal Plasticity; Neurons; Numbers; Organism; Output; Pain; Pathway interactions; Physiological; Plastics; Proteins; Retinal Degeneration; Sensory; Signal Pathway; Signal Transduction; Site; Stimulus; Temperature; Temperature Sense; Vertebrates; Visual; base; experience; gene function; intracellular protein transport; mutant; postsynaptic; protein localization location; response; sensory mechanism

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.

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。本研究旨在阐明C. elegans从基因到行为输出，以便更好地理解感觉信号转导和可塑性的机制。C.秀丽线虫感知温度，并产生对该温度的“记忆”，这反过来又决定了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，并且可以在暴露于新的温度时重置。为了更好地了解这种感觉方式和感觉可塑性一般，新开发的定量行为测定将被用来确定候选分子的贡献，从而概述了潜在的遗传和生化途径负责热敏行为。还将利用钙成像来确定这些候选分子在分子途径中的何处起作用。最后，将观察候选蛋白质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何处起作用以介导适当的行为。这些方法的结合将提供第一个全面的分析保守分子参与定义方面的热敏性和可塑性。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的缺陷引起的。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有很多了解，但温度感觉的特征仍然很差。探讨C.线虫将鉴定在多种生物体中可能在感觉信号转导中保守的感觉分子的功能。C.秀丽隐杆线虫在其热敏反应中也表现出长期可塑性。神经元可塑性的刺激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C. elegans将揭示涉及高等生物神经系统的保守分子和机制。