{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:50:37Z","timestamp":1788922237181,"version":"build-2803163510"},"reference-count":84,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/09734-6"],"award-info":[{"award-number":["2022\/09734-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/05299-0"],"award-info":[{"award-number":["2021\/05299-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/09768-5"],"award-info":[{"award-number":["2021\/09768-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/07705-9"],"award-info":[{"award-number":["2022\/07705-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K99HL168211"],"award-info":[{"award-number":["K99HL168211"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL151389"],"award-info":[{"award-number":["R01HL151389"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL126523"],"award-info":[{"award-number":["R01HL126523"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL144801"],"award-info":[{"award-number":["R01HL144801"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306580\/2023-3"],"award-info":[{"award-number":["306580\/2023-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306418\/2023-1"],"award-info":[{"award-number":["306418\/2023-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:p>\n                    Opioid-induced respiratory depression (OIRD) suppresses breathing and destabilizes ventilation. Using optogenetic and chemogenetic tools, we demonstrated that stimulating retrotrapezoid nucleus (RTN) Phox2b\n                    <jats:sup>+<\/jats:sup>\n                    \/ Nmb\n                    <jats:sup>+<\/jats:sup>\n                    neurons enhances breathing, even after fentanyl administration, whereas their inhibition exacerbates hypoventilation. These findings reveal that RTN neurons retain their ability to drive ventilation during OIRD, highlighting their potential as a therapeutic target to restore respiratory function in opioid overdose cases.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00025.2025","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T01:00:02Z","timestamp":1753232402000},"page":"L357-L375","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Functional modulation of retrotrapezoid neurons drives fentanyl-induced respiratory depression"],"prefix":"10.1152","volume":"329","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-8296","authenticated-orcid":false,"given":"Thiago S.","family":"Moreira","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Sao Paulo","place":["Brazil"]},{"name":"Seattle Children\u2019s Research Institute","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7986-4247","authenticated-orcid":false,"given":"Nicholas J.","family":"Burgraff","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["United States"]},{"name":"University of Wisconsin-Madison","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-0760","authenticated-orcid":false,"given":"Ana C.","family":"Takakura","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["United States"]},{"name":"University of Sao Paulo","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-4572","authenticated-orcid":false,"given":"Luiz M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-2722","authenticated-orcid":false,"given":"Emmanuel V.","family":"de Araujo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Sao Paulo","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Guan","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5626-3999","authenticated-orcid":false,"given":"Jan-Marino","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["United States"]},{"name":"University of Washington","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-022-03300-7"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022134118"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen094"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6614a2"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6643e1"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00819.2021"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4103\/ija.ija_171_22"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1177\/23247096211034036"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1113\/JP285163"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.13484"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90458-L"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100069"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140004"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22769"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2018.07.003"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00125-0"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature16964"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.01.019"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40812-x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107779"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1996.270.6.r1273"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2012.12.002"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.08.001"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nn1357"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.103788"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2917-06.2006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.153163"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.11.031"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1113\/JP275866"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00478.2023"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.09.002"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00497.2020"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2055-17.2017"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121095119"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1046-12.2013"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2114-20.2021"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1113\/EP087507"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4639-10.2011"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52572"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1113\/JP281545"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.09.015"},{"key":"B42","volume-title":"Paxinos and Franklin\u2019s the Mouse Brain in Stereotaxic Coordinates, Compact","author":"Franklin K","year":"2019"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1109\/tsmc.1978.4310039"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0386-23.2023"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00866"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2048-18.2018"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2022.108313"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.94653"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01061.2010"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22136"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ng1130"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5550-12.2013"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3280-11.2011"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2013.076752"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2012.065128"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.020032"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.177535"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1106-09.2009"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1196"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00712.2009"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00150.2022"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67523"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15580"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1113\/JP278612"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1113\/JP270822"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52694"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1329-21.2021"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.05.020"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c110057"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-91534-2.00010-2"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/s1357-2725(03)00050-5"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00194.2017"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0045-15.2015"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.932189"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81119"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1902"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780195306637.003.0002"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-009-0645-3"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-91534-2.00003-5"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-015-1734-0"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00265.2015"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2005.031922"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.02.004"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318224cc1f"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajplung.00025.2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T14:24:57Z","timestamp":1757859897000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajplung.00025.2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":84,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9,1]]}},"alternative-id":["10.1152\/ajplung.00025.2025"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00025.2025","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.28.635295","asserted-by":"object"}]},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,1]]},"assertion":[{"value":"2025-01-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-16","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}