{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:32:39Z","timestamp":1792045959473,"version":"4.4.0"},"reference-count":74,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T00:00:00Z","timestamp":1514332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL108609"],"award-info":[{"award-number":["HL108609"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL074011"],"award-info":[{"award-number":["HL074011"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL28785"],"award-info":[{"award-number":["HL28785"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The retrotrapezoid nucleus (RTN) regulates breathing in a CO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010 and state\u2010dependent manner. RTN neurons are glutamatergic and innervate principally the respiratory pattern generator; they regulate multiple aspects of breathing, including active expiration, and maintain breathing automaticity during non\u2010REM sleep. RTN neurons encode arterial\n                    <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12737-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12737:tjp12737-math-0001\"\/>\n                    \/pH via cell\u2010autonomous and paracrine mechanisms, and via input from other CO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010responsive neurons. In short, RTN neurons are a pivotal structure for breathing automaticity and arterial\n                    <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12737-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12737:tjp12737-math-0002\"\/>\n                    homeostasis. The carotid bodies stimulate the respiratory pattern generator directly and indirectly by activating RTN via a neuronal projection originating within the solitary tract nucleus. The indirect pathway operates under normo\u2010 or hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons are silent and the excitatory input from the carotid bodies is suppressed. Also, silencing RTN neurons optogenetically quickly triggers a compensatory increase in carotid body activity. Thus, in conscious mammals, breathing is subject to a dual and interdependent feedback regulation by chemoreceptors. Depending on the circumstance, the activity of the carotid bodies and that of RTN vary in the same or the opposite directions, producing additive or countervailing effects on breathing. These interactions are mediated either via changes in blood gases or by brainstem neuronal connections, but their ultimate effect is invariably to minimize arterial\n                    <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12737-math-0003.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12737:tjp12737-math-0003\"\/>\n                    fluctuations. We discuss the potential relevance of this dual chemoreceptor feedback to cardiorespiratory abnormalities present in diseases in which the carotid bodies are hyperactive at rest, e.g. essential hypertension, obstructive sleep apnoea and heart failure.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp12737-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp274357","type":"journal-article","created":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T22:22:39Z","timestamp":1511389359000},"page":"3029-3042","source":"Crossref","is-referenced-by-count":49,"title":["Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1739-2306","authenticated-orcid":false,"given":"Patrice G.","family":"Guyenet","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Bayliss","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-8923","authenticated-orcid":false,"given":"Ruth L.","family":"Stornetta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Kanbar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Lebanese American University  Beyrouth Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B.","family":"Holloway","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M. P. R.","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler M.","family":"Basting","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Experimental Therapeutics Louisiana State University  New Orleans Louisiana 70112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B. G.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Wenker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Virginia  Charlottesville VA 22908 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,27]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3280-11.2011"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.167502"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.11.031"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272046"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2923-14.2015"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00960-3"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22769"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270053"},{"key":"e_1_2_2_10_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1242\/jeb.100.1.223","article-title":"Respiratory and circulatory control during sleep","volume":"100","author":"Coote JH","year":"1982","journal-title":"J Exp Biol"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040239"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(89)90078-9"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273335"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.07255"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.079"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2017.00009"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709115105"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256800"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01321.2009"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.210534"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.247304"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.4.1600"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29566"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00571"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910059107"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190721"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2004.05.004"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.08.001"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271480"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25232"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12996"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00855.2001"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2953-14.2015"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.14203"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.192088"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.098848"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4143-12.2013"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021263"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa0922"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100069"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3395"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.266221"},{"key":"e_1_2_2_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3141-10.2010"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.01.019"},{"key":"e_1_2_2_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00070.2011"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1357"},{"key":"e_1_2_2_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.3.262"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.9.1183"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.020032"},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63274-6.00004-7"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5338-10.2011"},{"key":"e_1_2_2_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.85.4.1299"},{"key":"e_1_2_2_53_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272708"},{"key":"e_1_2_2_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4173"},{"key":"e_1_2_2_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00022.2015"},{"key":"e_1_2_2_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1721-11.2011"},{"key":"e_1_2_2_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2005.03.018"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2013"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07051"},{"key":"e_1_2_2_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63274-6.00001-1"},{"key":"e_1_2_2_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2055-17.2017"},{"key":"e_1_2_2_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2011.209"},{"key":"e_1_2_2_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270114"},{"key":"e_1_2_2_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.79.3.689"},{"key":"e_1_2_2_65_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2013.076752"},{"key":"e_1_2_2_66_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.103788"},{"key":"e_1_2_2_67_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256818"},{"key":"e_1_2_2_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2354"},{"key":"e_1_2_2_69_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1281-16.2016"},{"key":"e_1_2_2_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2015.05.008"},{"key":"e_1_2_2_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5550-12.2013"},{"key":"e_1_2_2_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00544.2010"},{"key":"e_1_2_2_73_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.256578"},{"key":"e_1_2_2_74_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.110627"},{"key":"e_1_2_2_75_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.154187"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP274357","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP274357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:51:21Z","timestamp":1694685081000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP274357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,27]]},"references-count":74,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1113\/JP274357"],"URL":"https:\/\/doi.org\/10.1113\/jp274357","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732149913.793539764","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.732149913.793561212","asserted-by":"object"}]},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,27]]}}}