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Inhibitory control of the active expiratory pattern in rats submitted to chronic hypoxia

Grant number: 15/23568-8
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2016
Effective date (End): February 28, 2018
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Daniel Breseghello Zoccal
Grantee:Karine Correa Flor
Home 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

Abstract

Resting respiratory activity is generated by the synchronized activity of a complex neural respiratory network located in the brain stem, in which is inserted a primary respiratory oscillator essential for the respiratory rhythm. This oscillator is located in the ventral respiratory column and consists of auto-depolarizating inspiratory neurons. However, recent studies suggest the existence of a second respiratory oscillator, which appears to have a critical role in the generation of active expiratory pattern, as observed in conditions of hypoxia and hypercapnia. This expiratory oscillator is found rostral to the ventral respiratory column and ventral to the facial nucleus, in a region named parafacial respiratory group (pFRG). In addition to its important role in generating the expiratory pattern, the respiratory neurons of the pFRG appear to influence the generation of sympathetic activity, contributing to the coupled control of respiratory and sympathetic activities, especially under conditions of metabolic challenges. Studies suggest that the activation of the pFRG expiratory neurons depends on the balance between excitatory and inhibitory mechanisms. In this project, we will verify the contribution of inhibitory mechanisms for the emergence of active expiration pattern. Initially, we will explore the hypothesis that neurons of the Bötzinger complex (BötC) are an important inhibitory source controling the generation of active expiration pattern in naïve rats. Later, we will study the role of inhibitory mechanisms and the involvement of the BötC in the generation of active expiration in rats exposed to 10% O2 for 24 hours - condition which promotes the development of the active expiration pattern at rest. These possibilities will be explored using the in situ working heart-brainstem preparation, in which will record from respiratory and sympathetic motor nerves, as well as perform microinjections of pharmacological agonists and antagonists in the ventral surface of the medulla. (AU)