Synaptic transmission and electrophysiological properties of bronchial motoneurons of the dorsal motor nucleus of the vagus from rats

• Grant number: 19/11863-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2020
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Davi José de Almeida Moraes
• Grantee: Davi José de Almeida Moraes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The parasympathetic efferent innervation to the respiratory system controls mainly the contraction of the smooth muscle and mucous secretion in the lower airways. It is well known that the parasympathetic pre-ganglionic motoneurons, that project to the respiratory system, are found in the medulla, specifically in the Nucleus Ambiguus (NA) and in the Dorsal Motor Nucleus of the Vagus (DMV). The parasympathetic activity of the respiratory system is also modulated by sensorial neurons located throughout the respiratory airways, and such vagal afferences are transmitting information related the physical and chemical conditions of the airways and lungs to the central nervous system. However, our understanding of how vagal afferences are processed and integrated into the brainstem leading to respiratory changes (bronchospasm and mucous secretions) required for cough and dyspnea remains limited. Furthermore, it is not clear what are the neurotransmitters and cellular mechanisms underlining the central generation of parasympathetic activity to the bronchi by NA and DMV motoneurons in response to vagal afferent stimulation. The study of these mechanisms is critical, considering that the symptoms of the most common respiratory diseases (viral infections of the respiratory tract, rhinitis, bronchitis, asthma, COPD, chronic cough) are a consequence of changes in the nervous system. Thus, in order to improve our understanding of central cellular mechanisms involved in these pathological conditions, it is necessary to describe how motoneurons in the brainstem integrate the vagal sensorial afferences and control vagal motor bronchoconstrictor responses. For this purpose, we will apply the whole cell patch clamp technique, retrograde labelling and genetic manipulation (optogenetics) on brainstem slices and on in situ preparations from rats to evaluate: I) the electrophysiological properties of the DMV parasympathetic bronchial motoneurons, with emphasis on the control of their resting membrane potential and cellular excitability; II) how DMV parasympathetic bronchial motoneurons integrate the spontaneous synaptic transmission, that evoked by the stimulation of vagal afferents, and the neurotransmitters involved, and III) what is the role of DMV parasympathetic motoneurons in the control of lower airway resistance. The elucidation of these electrophysiological properties can promote a greater understanding about the cellular mechanisms involved in the central generation of the parasympathetic activity to the bronchi under physiological and pathological conditions, and even in the development of possible therapies aimed at the treatment of pathologies associated with dysfunctions in the afferent and efferent control of lower airways. (AU)

Scientific publications

(8)

(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.; SPILLER, PEDRO F.; PATON, JULIAN F. R.; MORAES, DAVI J. A.. Peripheral chemoreflex activation induces expiratory but not inspiratory excitation of C1 pre-sympathetic neurones of rats. ACTA PHYSIOLOGICA, v. N/A, p. 22-pg., 2022-06-28. (21/06886-7, 19/11863-6, 20/03955-5, 18/07027-5)

PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; ZOCCAL, DANIEL B.; ABDALA, ANA P.; SMITH, JEFFREY C.; ANTUNES, VAGNER R.; MURPHY, DAVID; DUTSCHMANN, MATHIAS; DHINGRA, RISHI R.; et al. Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years. JOURNAL OF PHYSIOLOGY-LONDON, v. 600, n. 9, p. 27-pg., 2022-04-07. (19/19894-8, 18/15957-2, 19/11863-6, 21/06886-7)

FELIPPE, IGOR S. A.; ZERA, TYMOTEUSZ; DA SILVA, MELINA P.; MORAES, DAVI J. A.; MCBRYDE, FIONA; PATON, JULIAN F. R.. The sympathetic nervous system exacerbates carotid body sensitivity in hypertension. Cardiovascular Research, v. N/A, p. 16-pg., 2022-01-20. (19/11863-6)

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)

LATARO, RENATA M.; MORAES, DAVI J. A.; GAVA, FABIO N.; OMOTO, ANA C. M.; SILVA, CARLOS A. A.; BROGNARA, FERNANDA; ALFLEN, LAIS; BRAZAO, VANIA; COLATO, RAFAELA PRAVATO; DO PRADO, JOSE' CLO'VIS; et al. P2X3 receptor antagonism attenuates the progression of heart failure. NATURE COMMUNICATIONS, v. 14, n. 1, p. 14-pg., 2023-03-28. (21/06886-7, 13/20549-7, 19/11863-6)

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)

MORAES, DAVI J. A.; DA SILVA, MELINA P.; DE SOUZA, DANIEL P.; FELINTRO, VIVIANE; PATON, JULIAN F. R.. Heightened respiratory-parasympathetic coupling to airways in the spontaneously hypertensive rat. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 12, p. 3237-3252, JUN 2021. (19/11863-6, 18/07027-5)

DOS SANTOS, KAROLINE MARTINS; MORAES, DAVI JOSE DE ALMEIDA; DA SILVA, MELINA PIRES; ANTUNES, VAGNER ROBERTO. Exercise training rescues the electrical activity of liver-projecting DMNV neurones in response to oxytocin in spontaneously hypertensive rats. Journal of Neuroendocrinology, v. 33, n. 5, MAY 2021. (16/21991-3, 19/11863-6)