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In aquatic vertebrates, oxygen sensing occurs in the gills via chemoreceptive neuroepithelial cells (NECs), but a mechanism for dopamine in autonomic control of ventilation has not been defined. We used immunohistochemistry and confocal microscopy to map the distribution of tyrosine hydroxylase (TH), an enzyme necessary for dopamine synthesis, in the gills of zebrafish. TH was found in nerve fibers of the gill filaments and respiratory lamellae. We further identified dopamine active transporter (\n                    <jats:italic>dat<\/jats:italic>\n                    ) and vesicular monoamine transporter (\n                    <jats:italic>vmat2<\/jats:italic>\n                    ) expression in neurons of the gill filaments using transgenic lines. Moreover, TH\u2010 and\n                    <jats:italic>dat<\/jats:italic>\n                    \u2010positive nerve fibers innervated NECs. In chemical screening assays, domperidone, a D\n                    <jats:sub>2<\/jats:sub>\n                    receptor antagonist, increased ventilation frequency in zebrafish larvae in a dose\u2010dependent manner. When larvae were confronted with acute hypoxia, the D\n                    <jats:sub>2<\/jats:sub>\n                    agonist, quinpirole, abolished the hyperventilatory response. Quantitative polymerase chain reaction confirmed expression of\n                    <jats:italic>drd2a<\/jats:italic>\n                    and\n                    <jats:italic>drd2b<\/jats:italic>\n                    (genes encoding D\n                    <jats:sub>2<\/jats:sub>\n                    receptors) in the gills, and their relative abundance decreased following acclimation to hypoxia for 48\u00a0h. We localized D\n                    <jats:sub>2<\/jats:sub>\n                    receptor immunoreactivity to NECs in the efferent gill filament epithelium, and a novel cell type in the afferent filament epithelium. We provide evidence for the synthesis and storage of dopamine by sensory nerve terminals that innervate NECs. We further suggest that D\n                    <jats:sub>2<\/jats:sub>\n                    receptors on presynaptic NECs provide a feedback mechanism that attenuates the chemoreceptor response to hypoxia. Our studies suggest that a fundamental, modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution.\n                  <\/jats:p>","DOI":"10.1002\/cne.25548","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T12:58:31Z","timestamp":1697288311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A role for dopamine in control of the hypoxic ventilatory response via D\n                    <sub>2<\/sub>\n                    receptors in the zebrafish gill"],"prefix":"10.1002","volume":"532","author":[{"given":"Maddison","family":"Reed","sequence":"first","affiliation":[{"name":"Department of Biology University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Biology University of Ottawa  Ottawa Ontario 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