Molecular and neuronal mechanisms of thermosensory behavior

描述（由申请人提供）：动物对环境温度的反应机制尚不完全清楚。秀丽隐杆线虫以一种复杂的、依赖经验的方式对环境温度作出反应。秀丽隐杆线虫在热梯度上的行为取决于其先前的温度历史。本研究的目的是确定秀丽隐杆线虫热感觉反应和行为可塑性的分子和神经元机制。具体而言，我们将：1)表征秀丽隐杆线虫热感觉行为不同方面所需的AFD热感神经元的分子和途径。我们已经使用定量行为和钙成像分析，解剖秀丽隐杆线虫的热感行为为几个潜在的组成部分。我们将使用这些分析来确定候选分子对热感反应的不同方面的贡献，并开始将这些分子置于遗传和生化途径中。2)确定驱动嗜冷倾向的热感觉神经元。神经元回路分析表明，除了AFD神经元外，还有一个热感觉神经元对温度有反应。我们将使用激光介导的破坏实验来识别这个神经元。3)识别和分析分子热传感器。我们将使用正向和反向遗传方法来识别分子热感受器。热感受器的功能将通过错表达和异源表达实验进一步验证。这项工作将发现参与热感觉、热感觉信号转导和神经元可塑性的新分子。我们期望类似的分子和机制在高等动物中运作，以调节多种情况下的神经系统功能，包括神经元疾病。概要：目标是识别使用秀丽隐杆线虫模型系统感知温度所需的分子和神经元。预计这些基因中的许多在包括人类在内的其他生物体中是保守的，并且在调节神经元功能方面发挥重要作用。

DESCRIPTION (provided by applicant): The mechanisms by which animals respond to environmental temperature is not fully understood. C. elegans responds to ambient temperature in a complex, experience-dependent manner. The behavior of C. elegans on a thermal gradient is dependent on its prior temperature history. The goal of this proposal is to define the molecular and neuronal mechanisms required for C. elegans thermosensory responses and behavioral plasticity. Specifically, we will: 1) Characterize the molecules and pathways in the AFD thermosensory neurons required for different aspects of C. elegans thermosensory behavior. We have used quantitative behavioral and calcium imaging assays to dissect C. elegans thermosensory behavior into several underlying components. We will use these assays to define the contributions of candidate molecules to different aspects of thermosensory responses, and begin to place these molecules in genetic and biochemical pathways. 2) Identify the thermosensory neuron driving a cryophilic bias. Neuronal circuit analyses indicate that a thermosensory neuron other than the AFD neurons responds to temperature. We will identify this neuron using laser-mediated disruption experiments. 3) Identify and analyze molecular thermosensors. We will use forward and reverse genetic approaches to identify molecular thermoreceptors. Thermoreceptor functions will be further validated by misexpression and heterologous expression experiments. This work will identify new molecules involved in thermosensation, thermosensory signal transduction and neuronal plasticity. We expect that similar molecules and mechanisms operate in higher animals to regulate nervous system function in multiple contexts, including in neuronal disorders. Lay summary: The goal is to identify molecules and neurons required for sensing temperature using the C. elegans model system. Many of these genes are expected to be conserved in other organisms including humans, and to play important roles in regulating neuron functions.