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Functional interaction between raphe and retrotrapezoid nuclei for the control of breathing pattern and hypercapnic ventilatory response in rats

Grant number: 18/04439-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): January 01, 2019
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Débora Simões de Almeida Colombari
Grantee:Isabela de Paula Leirão
Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:13/17251-6 - Neural mechanisms generating the respiratory pattern and the respiratory-sympathetic coupling in conditions of hypoxia, AP.JP


Breathing is an automatic homeostatic process, primarily coordinated by a complex neural network located in the brainstem. The functioning of this neural network is modified during stimuli that promote alterations in the partial pressure of the blood gases. In hypercapnia (increase in PaCO2), chemosensory cells located in the brainstem, which are directly connected to the respiratory neural network, are stimulated and send excitatory inputs to the respiratory neurons to trigger responses of hyperventilation. Among the candidates responsible for central chemoreception are the Raphe serotonergic neurons. Serotonin is an important neuromodulator capable of regulating the excitability of respiratory neurons, modifying the operation of the respiratory network. In addition to possessing intrinsic chemosensitivity characteristics (sensitive to CO2 and pH variations), experimental evidence shows that inhibition of Raphe serotonergic neurons attenuates ventilatory responses to hypercapnia, supporting the concept that Raphe neurons are central chemoreceptors and contribute to reflex ventilatory responses. However, there is no functional evidence for how Raphe serotonergic neurons interact with the respiratory network. Based on evidence from the literature, in this project we will explore the hypothesis that, under conditions of hypercapnia, Raphe serotonergic neurons are stimulated and contribute to the reflex ventilatory response, at least in part, by stimulating the chemosensitive neurons present in the retrotrapezoid nucleus (RTN) - an important respiratory region located on the medullary ventral surface. For this, we will perform measurements of pulmonary ventilation in vivo, and recordings of inspiratory and expiratory motor activity in situ, during resting and hypercapnic conditions, in rats that will receive microinjections of serotonin receptor-conjugated saporin toxin (Anti-SERT-SAP) in the RTN, in order to promote the selective lesion of the serotoninergic projections to this nucleus.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LEIRAO, ISABELA P.; COLOMBARI, DEBORA S. A.; DA SILVA, GLAUBER S. F.; ZOCCAL, DANIEL B.. Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals. Neuroscience, v. 452, p. 63-77, . (18/21000-2, 13/17251-6, 18/04439-0)

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