{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:40:35Z","timestamp":1791398435282,"version":"4.3.3"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,4,5]],"date-time":"2006-04-05T00:00:00Z","timestamp":1144195200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:p>The rat retrotrapezoid nucleus (RTN) contains pH\u2010sensitive neurons that are putative central chemoreceptors. Here, we examined whether these neurons respond to peripheral chemoreceptor stimulation and whether the input is direct from the solitary tract nucleus (NTS) or indirect via the respiratory network. A dense neuronal projection from commissural NTS (commNTS) to RTN was revealed using the anterograde tracer biotinylated dextran amine (BDA). Within RTN, 51% of BDA\u2010labelled axonal varicosities contained detectable levels of vesicular glutamate transporter\u20102 (VGLUT2) but only 5% contained glutamic acid decarboxylase\u201067 (GAD67). Awake rats were exposed to hypoxia (<jats:italic>n<\/jats:italic>= 6) or normoxia (<jats:italic>n<\/jats:italic>= 5) 1 week after injection of the retrograde tracer cholera toxin B (CTB) into RTN. Hypoxia\u2010activated neurons were identified by the presence of Fos\u2010immunoreactive nuclei. CommNTS neurons immunoreactive for both Fos and CTB were found only in hypoxia\u2010treated rats. VGLUT2 mRNA was detected in 92 \u00b1 13% of these neurons whereas only 12 \u00b1 9% contained GAD67 mRNA. In urethane\u2013chloralose\u2010anaesthetized rats, bilateral inhibition of the RTN with muscimol eliminated the phrenic nerve discharge (PND) at rest, during hyperoxic hypercapnia (10% CO<jats:sub>2<\/jats:sub>), and during peripheral chemoreceptor stimulation (hypoxia and\/or <jats:sc>i.v.<\/jats:sc> sodium cyanide, NaCN). RTN CO<jats:sub>2<\/jats:sub>\u2010activated neurons were recorded extracellularly in anaesthetized intact or vagotomized rats. These neurons were strongly activated by hypoxia (10\u201315% O<jats:sub>2<\/jats:sub>; 30 s) or by NaCN. Hypoxia and NaCN were ineffective in rats with carotid chemoreceptor denervation. Bilateral injection of muscimol into the ventral respiratory column 1.5 mm caudal to RTN eliminated PND and the respiratory modulation of RTN neurons. Muscimol did not change the threshold and sensitivity of RTN neurons to hyperoxic hypercapnia nor their activation by peripheral chemoreceptor stimulation. In conclusion, RTN neurons respond to brain <jats:styled-content><jats:italic>P<\/jats:italic><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-sub-5.gif\" xlink:title=\"urn:x-wiley:00223751:media:TJP1406:tex2gif-sub-5\"\/><\/jats:styled-content> presumably via their intrinsic chemosensitivity and to carotid chemoreceptor activation via a direct glutamatergic pathway from commNTS that bypasses the respiratory network. RTN neurons probably contribute a portion of the chemical drive to breathe.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.103788","type":"journal-article","created":{"date-parts":[[2006,2,3]],"date-time":"2006-02-03T01:32:29Z","timestamp":1138930349000},"page":"503-523","source":"Crossref","is-referenced-by-count":311,"title":["Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO<sub>2<\/sub>\u2010sensitive neurons in rats"],"prefix":"10.1113","volume":"572","author":[{"given":"Ana Carolina Thomaz","family":"Takakura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Santos","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Colombari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin 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