143 Individual Vagus Nerve Sensory Neurons Respond Distinctly to Specific Pro-inflammatory Cytokines

Abstract

INTRODUCTION: The peripheral nervous system (PNS) communicates with the immune system in response to injury or infection. In the case of inflammation, sensory signals travel up to the brain via the vagus nerve, which is a major pathway for neuro-immune communication. While our previous work showed that systemic cytokine administration was associated with specific patterns of vagus nerve activity, we did not know how individual vagal sensory neurons encoded this immune information. Here, we use invivo calcium imaging to monitor the neural activity of individual vagal sensory neurons in response to specific inflammatory mediators. METHODS: Using mice that express the calcium sensor GCaMP6f in glutamatergic neurons, we imaged neurons of the nodose ganglion in-vivo using a 1-photon miniature microscope (Miniscope). During imaging, the inflammatory mediator tumor necrosis factor (TNF) and interleukin 1β (IL-1β) were applied directly to the vagus nerve. The fluorescence data were analyzed with Python-based calcium imaging analysis (CaImAn) software and customized pipelines to output the neural activity as the normalized change in fluorescence (DFF) individually detected neurons. RESULTS: Our results reveal that specific vagal sensory neurons respond differentially to specific immune mediators. The average amplitude, and integral of TNF-responsive neurons were significantly higher than IL-1β-responsive cells (TNF vs IL-1β, p < 0.01). This result suggests that TNF application triggers higher firing rates for a more prolonged time in TNF-responsive neurons compared to IL-1β specific responses. Neuronal responses to IL-1β had a significantly higher number of peaks when compared to TNF responses (IL-1β vs TNF, p < 0.05). CONCLUSIONS: Our findings demonstrate that individual vagal sensory neurons encode information about distinct inflammatory stimuli and provide insight into the neural sensing of inflammation. Further investigation into neuro-immune signaling may identify novel neural targets for the treatment of inflammatory disorders.