An Integrated Approach to Understanding Temperature Sensation and Its Behavioral Consequences

体温对动物生物学的各个方面都有深远的影响。所有动物，包括人类，都有能力通过移动到环境中有利的区域来调节自己的体温。这种行为体温调节被认为涉及皮肤中的温度感觉神经元、内部设定点和复杂的反馈。理解行为体温调节的一个主要挑战是识别能够接受机械分析的动物。线虫只有302个神经细胞(神经元)，是进行此类研究的几乎完美的有机体。它是唯一一种已知每个神经元的形状及其与其他神经元的连接的动物(接线图)。一个由11个两侧对称神经元组成的子回路负责调节对温度的初始反应。所有这些神经元都可以在活着的动物身上找到，包括一对感受冷暖的神经元(AFD细胞)，它们对趋热性至关重要。在线虫中，但在哺乳动物中，可以直接测量这些神经元对温度的反应。这项拟议的研究利用了线虫的这些优势，并采取了一种综合的方法，在分子和细胞水平上分析温度感觉。有人提议进行实验，以解构使温度感觉成为可能的分子网络，并发现负责将感觉与行为联系起来的神经元的发育或功能的基因。由于接线图已知，未来的实验可以研究将AFD的温度感觉与电机输出联系起来的神经电路。在线虫中，AFD神经元是成功趋热的关键。其他线虫是农业上重要动植物的寄生虫，被认为是利用趋热性作为寻找宿主策略的一部分。这些寄生线虫中的一些已知具有与AFD相似的神经元，这表明拟议的研究可能具有更广泛的影响。特别是，对影响温度的分子网络的了解可以为控制威胁农业的线虫物种的方法提供新的研究切入点。这项工作的学术价值在于建立了一种新的动物模型，用于温度感觉及其行为后果的机理分析。它有可能提供对普遍的分子、细胞和网络级别的机制的洞察，通过这些机制，感觉信息为运动提供必要的实时反馈。这项工作从它的多学科方法中获得了广泛的影响，结合了遗传学、细胞生理学和行为研究的实验和概念工具。自该项目成立以来，高中生和本科生为这项工作做出了贡献，其中包括斯坦福大学夏季研究项目的女性和少数族裔参与者。本科生的研究机会将继续是拟议工作的一个组成部分。此外，国际和平协会鼓励实验室成员参加社区外展活动，并为这项重要工作提供释放时间。

Body temperature has profound influences on all aspects of animal biology. All animals, including humans, have the ability to regulate their body temperature by moving to favorable areas in the environment. This behavioral thermoregulation is thought to involve thermosensory neurons in the skin, an internal set point and complex feedback. A major challenge in understanding behavioral thermoregulation is to identify animals amenable to mechanistic analysis. With only 302 nerve cells (neurons), the roundworm C. elegans is an almost perfect organism for such studies. It is the only animal in which the shape of every neuron and its connections to other neurons is known (the wiring diagram). A sub-circuit of 11 bilaterallysymmetric neurons mediate initial responses to temperature. All of these neurons can be identified in living animals, including a pair of neurons that sense cooling and warming (the AFD cells) and are critical for thermotaxis. In C. elegans, but not in mammals, it is possible to directly measure how these neurons respond to temperature. The proposed research leverages these advantages of C. elegans and takes an integrated approach, analyzing temperature sensation at the molecular and cellular level. Experiments are proposed to deconstruct the molecular networks that make temperature sensation possible and to discover genes responsible for the development or function of neurons that link sensation to behavior. Because the wiring diagram is known, future experiments can investigate the neural circuit linking temperature sensation by AFD to motor output. In C. elegans, the AFD neurons are critical for successful thermotaxis. Other nematodes, which are parasites of agriculturally important plants and animals, are thought to use thermotaxis as part of a host-finding strategy. Some of these parasitic nematodes are known to have neurons similar to AFD, suggesting that the proposed research could have broader implications. In particular, what is learned about the molecular networks responsible for temperature could provide entry points for new research into methods for controlling nematode species that threaten agriculture. The intellectual merit of this work lies in the establishment of a new animal model for mechanistic analysis of temperature sensation and its behavioral consequences. It has the potential to offer insight into universal molecular, cellular and network-level mechanisms by which sensory information provides essential, real-time feedback for movement. The work derives broad impact from its multidisciplinary approach, combining the experimental and conceptual tools of genetics, cell physiology, and behavioral studies. Since its inception, high school students and undergraduates have contributed to the work, including women and minority participants in the Stanford Summer Research Program. Research opportunities for undergraduates will continue to be an integral part of the proposed work. Additionally, the PI encourages lab members to participate in community outreach activities and provides release time for this important work.