Molecular and neuronal mechanisms of thermosensory behavior

描述(申请人提供)：动物对环境温度的反应机制尚不完全清楚。线虫以一种复杂的、依赖经验的方式对环境温度做出反应。线虫在温度梯度上的行为取决于其先前的温度历史。这项建议的目的是确定线虫温度感觉反应和行为可塑性所需的分子和神经机制。具体地说，我们将：1)表征AFD温敏神经元中不同方面的线虫温敏行为所需的分子和途径。我们已经使用定量行为和钙成像分析方法将线虫的热敏行为分解成几个潜在的成分。我们将使用这些分析来确定候选分子对热敏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)确定驱动嗜冷性偏向的温敏神经元。神经元回路分析表明，除AFD神经元外，还有其他热敏神经元对温度做出反应。我们将使用激光介导的破坏实验来识别这种神经元。3)分子热敏传感器的鉴定与分析。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。这项工作将识别参与温度感觉、温度感觉信号转导和神经元可塑性的新分子。我们预计，在高等动物中，类似的分子和机制可以在多种情况下调节神经系统功能，包括在神经元障碍中。层层总结：目标是利用线虫模型系统识别传感温度所需的分子和神经元。其中许多基因有望在包括人类在内的其他生物中保守，并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.