Project Summary This is the same as the parent award. 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. Detection of immune mediators in the periphery, such as cytokines, is thought to be vagally-mediated but it is unclear how sensory neurons respond and represent this information in situ. The goal of the proposed studies is to discover how vagal sensory neurons encode and represent information about specific inflammatory mediators. This new understanding will provide crucial mechanistic insights into the nervous system representation of immune signals, 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 genetically encoded calcium indicators to monitor large groups of vagal sensory neurons while they respond to specific inflammatory mediators. We will use techniques and tools adopted from neuroscience to determine whether these neurons encode information using a population code or a temporal code for representing information immune-relevant information.