TY - JOUR TI - CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture AU - Forsberg, David AU - Horn, Zachi AU - Tserga, Evangelia AU - Smedler, Erik AU - Silberberg, Gilad AU - Shvarev, Yuri AU - Kaila, Kai AU - Uhlén, Per AU - Herlenius, Eric A2 - Ramirez, Jan-Marino VL - 5 PY - 2016 DA - 2016/07/05 SP - e14170 C1 - eLife 2016;5:e14170 DO - 10.7554/eLife.14170 UR - https://doi.org/10.7554/eLife.14170 AB - Inflammation-induced release of prostaglandin E2 (PGE2) changes breathing patterns and the response to CO2 levels. This may have fatal consequences in newborn babies and result in sudden infant death. To elucidate the underlying mechanisms, we present a novel breathing brainstem organotypic culture that generates rhythmic neural network and motor activity for 3 weeks. We show that increased CO2 elicits a gap junction-dependent release of PGE2. This alters neural network activity in the preBötzinger rhythm-generating complex and in the chemosensitive brainstem respiratory regions, thereby increasing sigh frequency and the depth of inspiration. We used mice lacking eicosanoid prostanoid 3 receptors (EP3R), breathing brainstem organotypic slices and optogenetic inhibition of EP3R+/+ cells to demonstrate that the EP3R is important for the ventilatory response to hypercapnia. Our study identifies a novel pathway linking the inflammatory and respiratory systems, with implications for inspiration and sighs throughout life, and the ability to autoresuscitate when breathing fails. KW - respiration KW - prostaglandins KW - neural network KW - chemosensitivity KW - calcium imaging KW - small world JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -