PT - JOURNAL ARTICLE AU - Alexander Klimovich AU - Stefania Giacomello AU - Åsa Björklund AU - Louis Faure AU - Marketa Kaucka AU - Christoph Giez AU - Andrea P. Murillo-Rincon AU - Ann-Sophie Matt AU - Gabriele Crupi AU - Jaime de Anda AU - Gerard C.L. Wong AU - Mauro D’Amato AU - Igor Adameyko AU - Thomas C.G. Bosch TI - Prototypical pacemaker neurons are immunocompetent cells AID - 10.1101/750026 DP - 2019 Jan 01 TA - bioRxiv PG - 750026 4099 - http://biorxiv.org/content/early/2019/08/30/750026.short 4100 - http://biorxiv.org/content/early/2019/08/30/750026.full AB - Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to generate rhythmic bursts of action potential. Recent work has identified rhythmic gut contractions in human, mice and hydra to be dependent on both neurons and the resident microbiota. However, little is known about the evolutionary origin of these neurons and their interaction with microbes. In this study, we identified and functionally characterized prototypical ANO/SCN/TRPM ion channel expressing pacemaker cells in the basal metazoan Hydra by using a combination of single-cell transcriptomics, immunochemistry, and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a rich set of immune-related genes mediating their interaction with the microbial environment. Functional experiments validated a model of the evolutionary emergence of pacemaker cells as neurons using components of innate immunity to interact with the microbial environment and ion channels to generate rhythmic contractions.