{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:14:50Z","timestamp":1790327690814,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T00:00:00Z","timestamp":1392163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>This study was designed to investigate whether the Phox2b\u2010expressing neurons in the retrotrapezoid nucleus are important to breathing and chemoreflexes in conscious rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>The high rate of destruction of a defined cell population (Phox2b<jats:sup>+<\/jats:sup>TH<jats:sup>\u2212<\/jats:sup>) of the retrotrapezoid nucleus by the toxin suggests that the specialized connectivity of retrotrapezoid nucleus neurons, their glutamatergic nature and their relatively high sensitivity to CO<jats:sub>2<\/jats:sub> are determinant factors in explaining their large contribution to the central and peripheral chemoreflexes.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Chemoreception is the classic mechanism by which the brain regulates breathing in response to changes in tissue CO<jats:sub>2<\/jats:sub>\/H<jats:sup>+<\/jats:sup>. A brainstem region called the retrotrapezoid nucleus (RTN) contains a population of Phox2b\u2010expressing glutamatergic neurons that appear to function as important chemoreceptors. In the present study, we ask whether the destruction of a type of pH\u2010sensitive interneuron that expresses the transcription factor Phox2b and is non\u2010catecholaminergic (Phox2b<jats:sup>+<\/jats:sup>TH<jats:sup>\u2212<\/jats:sup>) could affect breathing in conscious adult rats. The injection of substance\u00a0P (1\u00a0nmol in a volume of 50\u00a0nl) into the RTN increased respiratory frequency, tidal volume, minute ventilation and mean arterial pressure. Bilateral injections of the toxin substance\u00a0P conjugated with saporin (SSP\u2013SAP) into the RTN destroyed Phox2b<jats:sup>+<\/jats:sup>TH<jats:sup>\u2212<\/jats:sup> neurons but spared facial motoneurons, catecholaminergic and serotonergic neurons and the ventral respiratory column caudal to the facial motor nucleus. Bilateral inhibition of RTN neurons with SSP\u2013SAP (0.6\u00a0ng in 30\u00a0nl) reduced resting ventilation and the increase in ventilation produced by hypercapnia (7% CO<jats:sub>2<\/jats:sub>) in conscious rats with or without peripheral chemoreceptors. In anaesthetized rats with bilateral lesions of around 90% of the Phox2b<jats:sup>+<\/jats:sup>TH<jats:sup>\u2212<\/jats:sup> neurons, acute activation of the B\u00f6tzinger complex, the pre\u2010B\u00f6tzinger complex or the rostral ventral respiratory group with NMDA (5\u00a0pmol in 50\u00a0nl) elicited normal cardiorespiratory output. In conclusion, the destruction of the Phox2b<jats:sup>+<\/jats:sup>TH<jats:sup>\u2212<\/jats:sup> neurons is a plausible cause of the respiratory deficits observed after injection of SSP\u2013SAP into the RTN. Our results also suggest that RTN neurons activate facilitatory mechanisms important to the control of breathing in resting or hypercapnic conditions in conscious adult rats.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2013.076752","type":"journal-article","created":{"date-parts":[[2013,12,21]],"date-time":"2013-12-21T04:13:17Z","timestamp":1387599197000},"page":"571-585","source":"Crossref","is-referenced-by-count":87,"title":["Phox2b\u2010expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats"],"prefix":"10.1113","volume":"99","author":[{"given":"Ana C.","family":"Takakura","sequence":"first","affiliation":[{"name":"Department of Pharmacology Institute of Biomedical Science University of S\u00e3o Paulo (USP)  05508\u2010000 S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara 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