{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:26:45Z","timestamp":1790666805959,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T00:00:00Z","timestamp":1530144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL28785"],"award-info":[{"award-number":["HL28785"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            The retrotrapezoid nucleus (RTN) drives breathing proportionally to brain\n                            <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12969-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12969:tjp12969-math-0002\"\/>\n                            but its role during various states of vigilance needs clarification.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Under normoxia, RTN lesions increased the arterial\n                            <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12969-math-0003.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12969:tjp12969-math-0003\"\/>\n                            set\u2010point, lowered the\n                            <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12969-math-0004.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12969:tjp12969-math-0004\"\/>\n                            set\u2010point and reduced alveolar ventilation relative to CO\n                            <jats:sub>2<\/jats:sub>\n                            production. Tidal volume was reduced and breathing frequency increased to a comparable degree during wake, slow\u2010wave sleep and REM sleep. RTN lesions did not produce apnoeas or disordered breathing during sleep.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            RTN lesions in rats virtually eliminated the central respiratory chemoreflex (CRC) while preserving the cardiorespiratory responses to hypoxia; the relationship between CRC and number of surviving RTN\n                            <jats:italic>Nmb<\/jats:italic>\n                            neurons was an inverse exponential.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The CRC does not function without the RTN. In the quasi\u2010complete absence of the RTN and CRC, alveolar ventilation is reduced despite an increased drive to breathe from the carotid bodies.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The retrotrapezoid nucleus (RTN) is one of several CNS nuclei that contribute, in various capacities (e.g. CO\n                      <jats:sub>2<\/jats:sub>\n                      detection, neuronal modulation) to the central respiratory chemoreflex (CRC). Here we test how important the RTN is to PCO\n                      <jats:sub>2<\/jats:sub>\n                      homeostasis and breathing during sleep or wake. RTN\n                      <jats:italic>Nmb<\/jats:italic>\n                      \u2010positive neurons were killed with targeted microinjections of substance P\u2013saporin conjugate in adult rats. Under normoxia, rats with large RTN lesions (92\u00a0\u00b1\u00a04% cell loss) had normal blood pressure and arterial pH but were hypoxic (\u22128\u00a0mmHg PaO\n                      <jats:sub>2<\/jats:sub>\n                      ) and hypercapnic (+10\u00a0mmHg ). In resting conditions, minute volume (V\n                      <jats:sub>E<\/jats:sub>\n                      ) was normal but breathing frequency (\n                      <jats:italic>f<\/jats:italic>\n                      <jats:sub>R<\/jats:sub>\n                      ) was elevated and tidal volume (\n                      <jats:italic>V<\/jats:italic>\n                      <jats:sub>T<\/jats:sub>\n                      ) reduced. Resting O\n                      <jats:sub>2<\/jats:sub>\n                      consumption and CO\n                      <jats:sub>2<\/jats:sub>\n                      production were normal. The hypercapnic ventilatory reflex in 65% FiO\n                      <jats:sub>2<\/jats:sub>\n                      had an inverse exponential relationship with the number of surviving RTN neurons and was decreased by up to 92%. The hypoxic ventilatory reflex (HVR; FiO\n                      <jats:sub>2<\/jats:sub>\n                      21\u201310%) persisted after RTN lesions, hypoxia\u2010induced sighing was normal and hypoxia\u2010induced hypotension was reduced. In rats with RTN lesions, breathing was lowest during slow\u2010wave sleep, especially under hyperoxia, but apnoeas and sleep\u2010disordered breathing were not observed. In conclusion, near complete RTN destruction in rats virtually eliminates the CRC but the HVR persists and sighing and the state dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in V\n                      <jats:sub>E<\/jats:sub>\n                      but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnoea during slow\u2010wave sleep, even under hyperoxia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp275866","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T04:57:55Z","timestamp":1524027475000},"page":"2521-2545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Breathing regulation and blood gas homeostasis after near complete lesions of the retrotrapezoid nucleus in adult rats"],"prefix":"10.1113","volume":"596","author":[{"given":"George M. P. 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