Molecular and neuronal mechanisms of thermosensory behavior

描述（由申请人提供）：神经系统的主要作用是在过去的经验和当前条件下感知和整合外部和内部线索，并将此信息转化为行为输出。细胞内和细胞间的信号通路，神经元网络产生定义，但适应性行为还没有很好地理解。本文对中国对虾的温感行为进行了研究。elegans提供了一个极好的系统，在该系统中探索小的、硬连线的神经元网络产生高度复杂和依赖经验的行为的途径。C.线虫在温度梯度上的生长受其培养温度（Tc）的"记忆"控制，使得动物在相对于Tc的特定温度范围内表现出限定的行为。Tc记忆是可塑的，在新的温度下培养动物时可以重置。该提案的总体目标是描述热感觉神经元之间的感觉转导、可塑性和通信以经验和上下文依赖的方式产生鲁棒且灵活的行为的机制。具体目标是：1）检查CaMKI/IV介导的基因表达调节在AFD热敏神经元中设置Tc记忆中的作用。Tc记忆部分由AFD热敏神经元的反应阈值编码。这一目标将测试的假设，活性调节的变化，在AFD表达的信号传导基因的表达设置其响应阈值，这些变化是由CaMKI/IV级联介导的。 2)探索神经调节在设置ASI温觉神经元的操作范围中的作用。虽然AFD是唯一以前已知的热感觉神经元类型，我们现在已经表明，ASI感觉神经元也是热感觉的，并表现出Tc依赖的操作范围。ASI的工作范围可由AFD通过肽能神经调节来设定。该目标将利用高度定量的行为测定、体内成像和光遗传学操作来描述AFD向ASI发出信号以协调其响应范围的机制。 3)研究AWC温感神经元的热传导和可塑性机制。除了AFD和ASI，我们发现AWC嗅觉神经元也是热敏的。本研究的目的是确定AWC中热传导的分子机制，并探索AWC代表饥饿诱导的行为可塑性在电路中的位点的假设。 我们实验室的工作揭示了外围热敏处理的意外复杂性。拟议的实验将阐明多种类型的热敏神经元之间的协调和通信机制，以确保一致的行为输出。鉴于跨物种的信号通路、突触机制和电路功能的显著保守性，这项工作将提供有关更复杂神经系统中感觉处理和可塑性的新信息。

DESCRIPTION (provided by applicant): A major role of the nervous system is to sense and integrate external and internal cues in the context of past experience and current conditions, and translate this information into behavioral outputs. The intracellular and intercellular signaling pathways by which neuronal networks generate defined, yet adaptive behaviors are not well understood. The study of thermosensory behaviors in C. elegans provides an excellent system in which to explore the pathways by which a small, hard-wired neuronal network generates highly complex and experience-dependent behaviors. The behavior of C. elegans on a thermal gradient is governed by a 'memory' of its cultivation temperature (Tc), such that animals exhibit defined behaviors in specific temperature ranges relative to Tc. Tc memory is plastic and can be reset upon cultivation of animals at a new temperature. The overall goal of this proposal is to describe the mechanisms by which sensory transduction, plasticity and communication among thermosensory neurons generate robust, yet flexible behaviors in an experience- and context-dependent manner. The Specific Aims are to: 1) Examine the role of CaMKI/IV-mediated regulation of gene expression in setting Tc memory in the AFD thermosensory neurons. Tc memory is in part encoded by the response threshold of the AFD thermosensory neurons. This aim will test the hypothesis that activity-regulated changes in the expression of AFD-expressed signaling genes sets their response threshold, and that these changes are mediated by a CaMKI/IV cascade. 2) Explore the role of neuromodulation in setting the operating range of the ASI thermosensory neurons. Although AFD was the only previously known thermosensory neuron type, we have now shown that the ASI sensory neurons are also thermosensory, and exhibit a Tc-dependent operating range. The operating range of ASI may be set by AFD via peptidergic neuromodulation. This aim will utilize highly quantitative behavioral assays, in vivo imaging, and optogenetic manipulations to describe the mechanisms by which AFD signals to ASI to coordinate their response ranges. 3) Investigate mechanisms of thermotransduction and plasticity in the AWC thermosensory neurons. In addition to AFD and ASI, we showed that the AWC olfactory neurons are also thermosensory. The goal of this aim is to define molecular mechanisms of thermotransduction in AWC, and to explore the hypothesis that AWC represents the locus of starvation-induced behavioral plasticity in the circuit. Work from our lab has uncovered unexpected complexity in thermosensory processing at the periphery. The proposed experiments will elucidate the mechanisms by which coordination and communication among multiple thermosensory neuron types ensures a coherent behavioral output. Given the remarkable conservation of signaling pathways, synaptic mechanisms and circuit functions across species, this work will provide new information about sensory processing and plasticity in more complex nervous systems.