Neural and genetic mechanisms underlying behavior in C. elegans

项目摘要 我们研究的长期目标是了解感觉环境是如何调节动物行为的。 在这项提案中，我们将重点研究两种感觉模式的遗传和神经基础： 温度感应和渗透感应。感知温度和渗透压的能力对生命来说是必不可少的。 体温感觉和渗透感觉的缺陷会导致各种神经、肾脏和代谢紊乱。一个 在温度感觉和渗透感觉中起关键作用的是分子感觉受体，它检测热和 渗透的暗示。然而，感知寒冷温度的冷感应受体的分子同一性是 人们对此知之甚少。同样，到目前为止，还没有确定的渗透压感受器 后生生物。线虫是一种广泛应用于感官研究的遗传模式生物。 生物学。为了在恶劣的环境中生存，线虫进化出了丰富的感官系统。喜欢 在哺乳动物中，线虫具有温度和渗透性。在这里，我们建议调查 动物感觉温度的遗传和神经机制，特别是寒冷的温度 以线虫为模型的渗透压。为此，我们将采取多方面的方法，将 分子遗传学、行为分析、激光消融、全脑成像和电生理学。作为 温度感觉和渗透感觉的机制，特别是涉及感官受体的机制， 倾向于进化保守，拟议的工作将提供新的见解，让我们了解 人类的体温感觉和渗透感觉及其相关的神经、肾脏和代谢疾病。

Project Summary The long-term goal of our research is to understand how the sensory environment regulates animal behavior. In this proposal, we will focus on investigating the genetic and neural basis of two sensory modalities: thermosensation and osmosensation. The ability to sense temperature and osmolarity is essential for life. Defects in thermosensation and osmosensation cause various neurological, renal and metabolic disorders. A key player in thermosensation and osmosensation is the molecular sensory receptors that detect thermal and osmotic cues. However, the molecular identities of cold-sensing receptors that sense cold temperatures are poorly understood. Similarly, no osmolarity-sensing receptors have thus far been definitively identified in any metazoan organisms. C. elegans is a popular genetic model organism widely used for the study of sensory biology. To survive the harsh environment, C. elegans has evolved a rich repertoire of sensory systems. Like mammals, C. elegans possesses the sense of temperature and osmolarity. Here, we propose to investigate the genetic and neural mechanisms by which animals sense temperature, particularly cold temperature, as well as osmolarity using C. elegans as a model. To do so, we will take a multifaceted approach that integrates molecular genetics, behavioral analysis, laser ablation, whole-brain imaging, and electrophysiology. As the mechanisms underlying thermosensation and osmosensation, particularly those involving sensory receptors, tend to be evolutionarily conserved, the proposed work will provide novel insights into our understanding of thermosensation and osmosensation in humans and their related neurological, renal and metabolic disorders.