Contribution of the parafacial Respiratory Group to the inspiratory, expiratory and cardiovascular responses of rats to muscle afferent fiber stimulation

• Grant number: 19/24060-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2020
• End date: February 16, 2024
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Davi José de Almeida Moraes
• Grantee: Karolyne Silva Magalhães
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 21/15149-6 - Effect of sympathetic activation on blood flow within the carotid body of normo- and hypertensive rats, BE.EP.DR

Abstract

During basal conditions, breathing in mammals presents passive expiratory phase, with low activity of abdominal muscles. On the other hand, the exercise can recruit these expiratory muscles to produce active expiration. Active expiration in rats is dependent on the activity of neurons called late-Expiratory (late-E) located in the parafacial Respiratory Group (pFRG). During exercise, it is also possible to observe inspiratory and cardiovascular responses. These responses are dependent in part on the Exercise Muscle Reflex (EMR), mediated by two reflex mechanisms: the mechanoreflex and the metaborreflex, activated by muscle contraction. When activated, this reflex causes stimulation of the neurons located in the dorsal horn of the spinal cord, through afferent fibers, and consequently those located in the cardiovascular and respiratory centers in the brainstem. That is, the stimulation of afferent muscle fibers can evoke the EMR. However, the mechanisms responsible for the generation of active expiration, as well as the inspiratory and cardiovascular response during EMR activation are not yet fully established. In this sense, the hypotheses of the present research project are: (I) the stimulation of afferent muscle fibers, and consequently the EMR, in in situ preparations of rats evokes active expiration and inspiratory and cardiovascular responses; and (II) pFRG late-E neurons are involved in the central generation of active expiration and inspiratory and cardiovascular responses evoked by stimulation of afferent muscle fibers in rats. To test these hypotheses, we will analyze the expiratory, inspiratory and cardiovascular responses to stimulation of afferent muscle fibers, and consequently the EMR, before and after pFRG neurons silencing. These neurons will be selectively silenced acutely by Clozapine-N-Oxide (CNO) application following selective cellular transfection of these neurons in rats with an adeno-associated viral vector to express inhibitory G-protein-coupled receptors (hM4DiR) activated by CNO. We will also characterize the electrophysiological changes of pFRG late-E neurons in response to stimulation of afferent muscle fibers by whole cell patch clamp recordings in in situ preparations of rats. Besides, we will inject neuronal tracers into the rat´s medulla and spinal cord to investigate the afferent pathways of the EMR and its projection to pFRG. Thus, these results may contribute to a better understanding of afferent pathways involved in the central generation of inspiratory, expiratory and cardiovascular responses of rats to stimulation of afferent muscle fibers. (AU)

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)

DA SILVA, MELINA P.; MAGALHAES, KAROLYNE S.; DE SOUZA, DANIEL P.; MORAES, DAVI J. A.. Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 6, FEB 2021. (18/15957-2, 19/11863-6, 19/24060-9, 18/07027-5)

MAGALHAES, KAROLYNE S.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Intrinsic and synaptic mechanisms controlling the expiratory activity of excitatory lateral parafacial neurones of rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 21, OCT 2021. (19/24060-9, 18/15957-2, 19/11863-6, 18/07027-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MAGALHÃES, Karolyne Silva. Lateral parafacial region neurons: electrophysiological characteristics, active expiration generation and modulation of sympathetic activity and cardiovascular function. 2024. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.