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The Ventilatory Response to Hypercapnia in vivo Requires Serotoninergic Afferents to the Retrotrapezoid Nucleus
Author(s) -
Leirão Isabela P.,
Colombari Débora S.A.,
da Silva Glauber S.F.,
Zoccal Daniel B.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04637
Subject(s) - hypercapnia , serotonergic , microinjections , raphe , raphe nuclei , nucleus raphe magnus , ventilation (architecture) , anesthesia , chemoreceptor , brainstem , medicine , respiratory system , central chemoreceptors , neuroscience , endocrinology , serotonin , biology , microinjection , mechanical engineering , receptor , engineering
Chemosensory cells located in the brainstem are responsible to monitor the arterial levels of CO 2 /pH and provide excitatory inputs to the respiratory network to evoke a reflex increase in ventilation in conditions of hypercapnia. Among the candidates responsible for central chemoreception are the Raphe serotoninergic neurons. However, there is scarce functional evidence about the role of specific serotoninergic projections to the respiratory network and other chemosensitive sites. Herein, we explored the hypothesis that the hypercapnic ventilatory response in vivo requires, at least in part, the stimulation of the Raphe serotoninergic neurons that project to the retrotrapezoid nucleus (RTN) ‐ an important respiratory and CO 2 /pH chemosensitive region of the ventrolateral medulla. To reach this goal, pulmonary ventilation was evaluated under baseline conditions and during the exposure to hypercapnia (7% CO 2 ) in unanesthetized juvenile Holtzman rats (60–90 g) that received bilateral microinjections of the toxin anti‐SERT‐SAP (0.1 mM) in the RTN to selectively lesion serotoninergic neurons that send projections to this region. After 15 days of anti‐SERT‐SAP microinjections in the RTN (n=7), baseline respiratory frequency (Rf) and tidal volume (V T ) were similar to control rats that received vehicle microinjections (n= 9). On the other hand, the ablation of RTN‐projecting serotoninergic neurons markedly attenuated the CO 2 ‐induced response of increase in the Rf (P=0.001), but not in the V T . Our preliminary analyses suggest that the impaired tachypneic response to hypercapnia induced by anti‐SERT‐SAP microinjections in the RTN was associated with reduced number of serotoninergic neurons in the Raphe Obscurus (Rob) and Magnus (RMg), but not in the Raphe Pallidus. Overall, our data support the idea that interactions between the serotoninergic neurons of the Rob/RMg and the RTN neurons are necessary for the processing of the hypercapnic ventilatory response in unanesthetized conditions. Support or Funding Information Supported by FAPESP and CNPq