Identification of cytokine-specific sensory neural signals in murine vagus nerve activity recordings

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Abstract The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g. blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brain stem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β. These cytokine-mediated responses were subsequently decoded using a Naïve Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9±17.8%, chance level 33%). Recordings obtained in IL-1 receptor knockout mice were devoid of IL-1β related signals, but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β and distal lidocaine nerve block attenuated all vagus neural signals recorded. Using a novel methodological framework, the results obtained in this study suggest cytokine-specific information is present in sensory neural signals within the vagus nerve.