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

Author(s)

Leirao, Isabela P. ^[1] ; Colombari, Debora S. A. ^[1] ; da Silva, Glauber S. F. ^[2] ; Zoccal, Daniel B. ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Dept Physiol & Pathol, Sch Dent, Araraquara, SP - Brazil

^[2] Fed Univ Minas Gerais ICB UFMG, Dept Physiol & Biophys, Inst Biol Sci, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Neuroscience; v. 452, p. 63-77, JAN 1 2021.
• Web of Science Citations: 0

Abstract

Hypercapnia 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. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 18/21000-2 - Ionic mechanisms underlying the ATP-mediated respiratory stimulation: understanding the interaction between central oxygen sensors and rhythm-generating neurons
• Grantee: Daniel Breseghello Zoccal
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 13/17251-6 - Neural mechanisms generating the respiratory pattern and the respiratory-sympathetic coupling in conditions of hypoxia
• Grantee: Daniel Breseghello Zoccal
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/04439-0 - Functional interaction between raphe and retrotrapezoid nuclei for the control of breathing pattern and hypercapnic ventilatory response in rats
• Grantee: Isabela de Paula Leirão
• Support Opportunities: Scholarships in Brazil - Master