Vagus nerve sensory neurons have distinct neural responses to inflammatory mediators

Abstract

Abstract Cytokines are secreted signaling proteins that are important mediators of inflammation. While prior work has demonstrated that the level of cytokines can be regulated by nerve stimulation, the role of the nervous system in sensing these immune mediators is still poorly understood. During periods of inflammation, it has been shown that sensory signals travel up the vagus nerve to the brain. However, it is unclear how individual vagal sensory neurons encode specific immune information. Here we use in vivo calcium imaging of the nodose ganglion to monitor neural activity in individual vagus nerve sensory neurons in response to specific cytokines. Using mice that express the calcium indicator GCaMP6f in glutamatergic neurons, we imaged neurons of the nodose ganglion in situ using a 1-photon miniature microscope (Miniscope). During imaging, the proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor (TNF) were applied directly to the vagus nerve. Fluorescence data was analyzed with a Python-based software CaImAn and a custom pipeline to output the single neuron activity as change in fluorescence: ΔF/F. Our results reveal that specific vagal sensory neurons respond differentially to specific immune mediators. The average amplitude, integral, and delay of TNF-responsive neurons was significantly higher than IL-1β-responsive cells (TNF vs IL-1β, p < 0.01), while having less number of peaks per response (TNF vs IL-1β, p < 0.05). This may suggest different patterns of transient neural activity associated with each particular cytokine. Further investigation into this type of neuro-immune signaling may identify novel neural targets for the treatment of inflammatory disorders. This study was funded in part by NIH/NIGMS