Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats

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dc.contributor.authorTakakura, Ana C.
dc.contributor.authorBarna, Barbara F.
dc.contributor.authorCruz, Josiane C.
dc.contributor.authorColombari, Eduardo [UNESP]
dc.contributor.authorMoreira, Thiago S.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal da Paraíba (UFPB)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-12-03T13:10:48Z
dc.date.available2014-12-03T13:10:48Z
dc.date.issued2014-03-01
dc.description.abstractNew Findings What is the central question of this study? This study was designed to investigate whether the Phox2b-expressing neurons in the retrotrapezoid nucleus are important to breathing and chemoreflexes in conscious rats. What is the main finding and its importance? The high rate of destruction of a defined cell population (Phox2b(+)TH(-)) 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 CO2 are determinant factors in explaining their large contribution to the central and peripheral chemoreflexes.Chemoreception is the classic mechanism by which the brain regulates breathing in response to changes in tissue CO2/H+. A brainstem region called the retrotrapezoid nucleus (RTN) contains a population of Phox2b-expressing glutamatergic neurons that appear to function as important chemoreceptors. In the present study, we ask whether the destruction of a type of pH-sensitive interneuron that expresses the transcription factor Phox2b and is non-catecholaminergic (Phox2b(+)TH(-)) could affect breathing in conscious adult rats. The injection of substanceP (1nmol in a volume of 50nl) into the RTN increased respiratory frequency, tidal volume, minute ventilation and mean arterial pressure. Bilateral injections of the toxin substanceP conjugated with saporin (SSP-SAP) into the RTN destroyed Phox2b(+)TH(-) 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-SAP (0.6ng in 30nl) reduced resting ventilation and the increase in ventilation produced by hypercapnia (7% CO2) in conscious rats with or without peripheral chemoreceptors. In anaesthetized rats with bilateral lesions of around 90% of the Phox2b(+)TH(-) neurons, acute activation of the Botzinger complex, the pre-Botzinger complex or the rostral ventral respiratory group with NMDA (5pmol in 50nl) elicited normal cardiorespiratory output. In conclusion, the destruction of the Phox2b(+)TH(-) neurons is a plausible cause of the respiratory deficits observed after injection of SSP-SAP 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.en
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508900 Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, Brazil
dc.description.affiliationFed Univ Paraiba UFPB, Ctr Biotechnol, Dept Biotechnol, BR-58051900 Joao Pessoa, Paraiba, Brazil
dc.description.affiliationSao Paulo State Univ UNESP, Sch Dent, Dept Physiol & Pathol, BR-14801903 Araraquara, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ UNESP, Sch Dent, Dept Physiol & Pathol, BR-14801903 Araraquara, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent571-585
dc.identifierhttp://dx.doi.org/10.1113/expphysiol.2013.076752
dc.identifier.citationExperimental Physiology. Hoboken: Wiley-blackwell, v. 99, n. 3, p. 571-585, 2014.
dc.identifier.doi10.1113/expphysiol.2013.076752
dc.identifier.issn0958-0670
dc.identifier.lattes4544450092427426
dc.identifier.urihttp://hdl.handle.net/11449/112527
dc.identifier.wosWOS:000332139900014
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofExperimental Physiology
dc.relation.ispartofjcr2.732
dc.relation.ispartofsjr1,238
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titlePhox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious ratsen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-Blackwell
unesp.author.lattes4544450092427426[4]
unesp.author.orcid0000-0002-1395-4036[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araraquarapt

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