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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 preB\u00f6tzinger 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.<\/jats:p>","DOI":"10.7554\/elife.14170","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T19:59:53Z","timestamp":1467057593000},"source":"Crossref","is-referenced-by-count":48,"title":["CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture"],"prefix":"10.7554","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4719-2201","authenticated-orcid":true,"given":"David","family":"Forsberg","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden"},{"name":"Karolinska University Hospital, Stockholm, 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