Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals

dc.contributor.authorLeirão, Isabela P. [UNESP]
dc.contributor.authorColombari, Débora S.A. [UNESP]
dc.contributor.authorda Silva, Glauber S.F.
dc.contributor.authorZoccal, Daniel B. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.date.accessioned2021-06-25T10:17:40Z
dc.date.available2021-06-25T10:17:40Z
dc.date.issued2021-01-01
dc.description.abstractHypercapnia promotes an increase in pulmonary ventilation due to the stimulation of brainstem chemosensory cells that are connected to the respiratory network. Among these cells are the raphe serotonergic neurons which widely send projections to distinct central respiratory compartments. Nevertheless, the physiological role of specific raphe serotonergic projections to other chemosensitive sites on the emergence of hypercapnia ventilatory response in vivo still remains to be elucidated. Here we investigated whether the ventilatory response to hypercapnia requires serotonergic inputs to the chemosensitive cells of the retrotrapezoid nucleus (RTN) in the ventrolateral medulla. To test this, pulmonary ventilation was evaluated under baseline conditions and during hypercapnia (7% CO2) in unanesthetized juvenile Holtzman rats (60–90 g) that received bilateral microinjections of either vehicle (control) or anti-SERT-SAP (0.1 mM, 10 pmol/100 nl) toxin in the RTN to retrogradely destroy serotonergic afferents to this region. Fifteen days after microinjections, baseline ventilation was not different between anti-SERT-SAP (n = 8) and control animals (n = 9). In contrast, the ablation of RTN-projecting serotonergic neurons markedly attenuated the hypercapnia-induced increase in respiratory frequency which was correlated with reduced numbers of serotonergic neurons in the raphe obscurus and magnus, but not in the raphe pallidus. The increase in tidal volume during hypercapnia was not significantly affected by anti-SERT-SAP microinjections in the RTN. Our data indicate that serotoninergic neurons that send projections to the RTN region are required for the processing of ventilatory reflex response during exposure to high CO2 in unanesthetized conditions.en
dc.description.affiliationDepartment of Physiology and Pathology School of Dentistry São Paulo State University (UNESP)
dc.description.affiliationDepartment of Physiology and Biophysics. Institute of Biological Sciences Federal University of Minas Gerais (ICB/UFMG)
dc.description.affiliationUnespDepartment of Physiology and Pathology School of Dentistry São Paulo State University (UNESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdCNPq: 132363/2018-6
dc.description.sponsorshipIdFAPESP: 2013/17251-6
dc.description.sponsorshipIdFAPESP: 2018/04439-0
dc.description.sponsorshipIdFAPESP: 2018/21000-2
dc.description.sponsorshipIdCNPq: 310331/2017-0
dc.description.sponsorshipIdCNPq: 403769/2016-7
dc.description.sponsorshipIdCNPq: 408950/2018-8
dc.format.extent63-77
dc.identifierhttp://dx.doi.org/10.1016/j.neuroscience.2020.11.005
dc.identifier.citationNeuroscience, v. 452, p. 63-77.
dc.identifier.doi10.1016/j.neuroscience.2020.11.005
dc.identifier.issn1873-7544
dc.identifier.issn0306-4522
dc.identifier.scopus2-s2.0-85097383359
dc.identifier.urihttp://hdl.handle.net/11449/205574
dc.language.isoeng
dc.relation.ispartofNeuroscience
dc.sourceScopus
dc.subjectcarbon dioxide
dc.subjectcentral chemoreception
dc.subjectmedullary raphe
dc.subjectventilation
dc.titleLesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animalsen
dc.typeArtigo

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