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未完全了解。C.秀丽线虫对环境温度的反应是复杂的，依赖于经验的。C.线虫在温度梯度上的生长取决于其先前的温度历史。该提案的目标是确定C. elegans热感觉反应和行为可塑性。具体而言，我们将：1）表征的分子和途径，在AFD热敏神经元所需的不同方面的C。线虫的热感觉行为我们使用定量行为和钙成像分析来解剖C。elegans热感觉行为分为几个基本组成部分。我们将使用这些测定来确定候选分子对热敏反应不同方面的贡献，并开始将这些分子置于遗传和生物化学途径中。2)识别驱动嗜冷偏向的温度感觉神经元。神经元回路分析表明，一个热敏神经元以外的AFD神经元响应温度。我们将使用激光介导的破坏实验来识别这种神经元。3)识别和分析分子温度传感器。我们将使用正向和反向遗传学方法来鉴定分子温度感受器。热感受器功能将通过错误表达和异源表达实验进一步验证。这项工作将确定新的分子参与温度感觉，温度感觉信号转导和神经可塑性。我们预计，类似的分子和机制在高等动物中发挥作用，以调节多种情况下的神经系统功能，包括神经元疾病。简单总结：我们的目标是确定分子和神经元所需的传感温度使用的C。elegans模型系统。这些基因中的许多基因预计在包括人类在内的其他生物体中是保守的，并在调节神经元功能中发挥重要作用。

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.