Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
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ABSTRACT:
SUBMITTER: Rosas-Ballina M
PROVIDER: S-EPMC4548937 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
Publications
Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
Rosas-Ballina Mauricio M Olofsson Peder S PS Ochani Mahendar M Valdés-Ferrer Sergio I SI Levine Yaakov A YA Reardon Colin C Tusche Michael W MW Pavlov Valentin A VA Andersson Ulf U Chavan Sangeeta S Mak Tak W TW Tracey Kevin J KJ
Science (New York, N.Y.) 20110915 6052
Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in choline ...[more]
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Project description: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 brainstem. IL-1? 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-1? 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-1? in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1? and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1?-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1?, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve.
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2023-10-25 | GSE246196 | GEO
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