Encoding of inflammatory mediators by vagal sensory neurons

项目摘要 神经系统和免疫系统相互沟通以应对感染 维持免疫系统的稳定过去二十年的研究表明，迷走神经 神经是携带运动信号下行的神经免疫通讯的关键通路 除了感官信号上升到大脑之外，这些途径包括 神经免疫反射回路中的两个弧称为炎症反射，其中神经活动 迷走神经上的神经节调节脾脏中细胞因子的产生。虽然功能和 脾的下行运动通路的分子机制在 这种反射，目前还不清楚迷走神经感觉神经元如何检测和代表信息， 原位炎症。这种未知的机制是一个关键的一部分，上升的感觉弧， 炎症反应因此，拟议研究的目标是使用大规模的钙 成像以发现迷走神经感觉神经元如何编码和表示特定的 炎症介质。通过监测迷走神经感觉神经元， 先天免疫应答的炎性介质（例如促炎和抗炎 细胞因子，DAMPs，PAMPs），我们的目标是揭示一个神经代码，无论是在人口水平， 单个感觉神经元的水平。这一新的理解将提供关键的机制 深入了解免疫信号的神经系统表示作为一般原则， 可以用来了解在一系列炎症性疾病中发生了什么， 免疫失调 我们有一个经验丰富的科学家团队，他们是免疫神经调节方面的专家， 将使用感觉神经科学的技术和方法来确定迷走神经 感觉神经元编码有关炎症介质的信息。这个新的基本原理 对神经免疫通讯的理解将潜在地提供新的机制见解 关于免疫稳态失调的问题它也可能导致新的识别 基于迷走神经的神经调节治疗多种炎性 紊乱

Project Summary The nervous system and immune system communicate with each other to respond to infections and maintain immune homeostasis. Work over the last two decades has shown that the vagus nerve is a critical pathway for neuro-immune communication carrying motor signals descending to the body, in addition to sensory signals ascending to the brain. These pathways comprise the two arcs in the neuro-immune reflex circuit termed the inflammatory reflex, in which neural activity on the vagus nerve regulates cytokine production in the spleen. While the functional and molecular mechanisms of the descending motor pathway to the spleen are well-established in this reflex, it is unclear how vagal sensory neurons detect and represent information about inflammation in situ. This unknown mechanism is a critical piece of the ascending sensory arc of the inflammatory reflex. Therefore, the goal of the proposed studies is to use large-scale calcium imaging to discover how vagal sensory neurons encode and represent information about specific inflammatory mediators. By monitoring vagal sensory neurons while they are presented with inflammatory mediators of the innate immune response (e.g. pro- and anti-inflammatory cytokines, DAMPs, PAMPs), we aim to uncover a neural code both at the population-level and at the level of individual sensory neurons. This new understanding will provide crucial mechanistic insights into the nervous system representation of immune signals as a general principle, which can be used to understand what goes wrong in a host of inflammatory disorders that involve immune dysregulation. With a team of experienced scientists who are experts in the neural regulation of immunity, we will use techniques and approaches adapted from sensory neuroscience to determine how vagal sensory neurons encode information about inflammatory mediators. This new fundamental understanding of neuro-immune communication will potentially provide new mechanistic insights about disorders of disrupted immune homeostasis. It may also lead to the identification of new targets and strategies for vagus nerve-based neuromodulation to treat a host of inflammatory disorders.