Electrophysiological and molecular characterization of neurons involved in the generation of respiratory rhythm and pattern of rats during postnatal development

• Grant number: 13/10484-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: July 01, 2014 - June 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• 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
• Associated researchers: Benedito Honorio Machado ; Wamberto Antonio Varanda
• Associated grant(s): 21/06886-7 - Role of purinergic receptors in the carotid body in heart failure, AP.JP2
• Associated scholarship(s): 17/20211-7 - Sustained hypoxia effects on electrophysiological properties of cardiac motoneurons of dorsal motor nucleus of vagus of rats, BP.IC; 16/24869-4 - Participation of lactate and carotid bodies in the respiratory responses of rats submitted to anaerobic physical exercise, BP.IC; 16/24994-3 - Participation of parafacial respiratory group in the orofacial and nasofacial motor responses of rats induced by activation of peripheral and central chemoreceptors, BP.IC; 14/13496-7 - Electrophysiological and molecular characterization of neurons involved in the generation of respiratory rhythm and pattern of rats during postnatal development., BP.JP

Abstract

The respiratory rhythm and respiratory pattern of three phases (inspiration, post-inspiration and second half of expiration) are generated by a neural network located in the ventral surface of the medulla, coordinated by synaptic interactions, specifically in the Parafacial Respiratory Group (pFRG), Bötzinger Complex (BötC) and the pre-Bötzinger Complex. (pre-BötC). Synaptic interactions between the neurons involved in the generation of respiratory rhythm and pattern in the ventral surface of the medulla have been the subject of intense research in the field of central control of respiration. However, the electrophysiological and molecular mechanisms of each neuron involved in the generation of respiratory rhythm and pattern are not fully understood and is one of the goals of this project. Furthermore, little is known about changes in electrophysiological and molecular mechanisms of different respiratory neurons during postnatal development, mechanisms that could explain the changes in respiratory rhythm and pattern in the different phases of the development. Thus, the aims of this project are to investigate the electrophysiological properties of different respiratory neurons of the ventral surface of medulla (pFRG, BötC and pre-BötC), the expression of voltage-dependent and leak channels that determine such electrophysiological properties and the morphology of these neurons during the postnatal development (P0-P40). The results to be obtained from this project, using advanced techniques of electrophysiology and molecular biology, will provide important functional information of how intrinsic electrophysiological properties and molecular profile of each group of respiratory neurons of the ventral surface of the medulla contribute to their firing patterns and consequently to the generation of respiratory rhythm and pattern during the postnatal development. (AU)

Scientific publications

(16)

(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.; MORAES, DAVI JOSE A.; BONAGAMBA, LENI G. H.; MECAWI, ANDRE DE SOUZA; VARANDA, WAMBERTO A.; MACHADO, BENEDITO H.. Hyperexcitability and plasticity induced by sustained hypoxia on rectus abdominis motoneurons. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1935-1956, APR 2019. (13/06077-5, 13/10484-5)

ROLOFF, EVA V. L.; WALAS, DAWID; MORAES, DAVI J. A.; KASPAROV, SERGEY; PATON, JULIAN F. R.. Differences in autonomic innervation to the vertebrobasilar arteries in spontaneously hypertensive and Wistar rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 596, n. 16, p. 3505-3529, AUG 15 2018. (13/10484-5)

MORAES, DAVI J. A.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 14, p. 3055-3063, JUL 15 2015. (13/06077-5, 13/10484-5)

DE BRITTO, ALAN A.; MORAES, DAVI J. A.. Non-chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 595, n. 6, p. 2043-2064, MAR 15 2017. (13/10484-5)

MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; ANTUNES-RODRIGUES, JOSE; MACHADO, BENEDITO H.. Respiratory Network Enhances the Sympathoinhibitory Component of Baroreflex of Rats Submitted to Chronic Intermittent Hypoxia. Hypertension, v. 68, n. 4, p. 1021-1030, OCT 2016. (13/06077-5, 13/10484-5)

MORAES, DAVI J. A.; MACHADO, BENEDITO H.. Electrophysiological properties of laryngeal motoneurones in rats submitted to chronic intermittent hypoxia. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 3, p. 619-634, FEB 1 2015. (13/06077-5, 13/10484-5)

DA SILVA, MELINA PIRES; DE ALMEIDA MORAES, DAVI JOSE; MECAWI, ANDRE DE SOUZA; RODRIGUES, JOSE ANTUNES; VARANDA, WAMBERTO ANTONIO. Nitric Oxide Modulates HCN Channels in Magnocellular Neurons of the Supraoptic Nucleus of Rats by an S-Nitrosylation-Dependent Mechanism. JOURNAL OF NEUROSCIENCE, v. 36, n. 44, p. 11320-11330, NOV 2 2016. (12/19750-7, 13/10484-5)

MAGALHAES, KAROLYNE S.; DE BRITTO, ALAN A.; PATON, JULIAN F. R.; MORAES, DAVI J. A.. A6 neurons simultaneously modulate active expiration and upper airway resistance in rats. Experimental Physiology, v. 105, n. 1, p. 53-64, JAN 2020. (17/09071-9, 16/24994-3, 13/10484-5)

DE BRITTO, ALAN A.; MAGALHAES, KAROLYNE S.; DA SILVA, MELINA P.; PATON, JULIAN F. R.; MORAES, DAVI J. A.. Active expiratory oscillator regulates nasofacial and oral motor activities in rats. Experimental Physiology, v. 105, n. 2, JAN 2020. (15/01073-7, 13/10484-5, 17/09071-9, 16/24994-3)

MORAES, DAVI J. A.; DA SILVA, MELINA P.; SPILLER, PEDRO F.; MACHADO, BENEDITO H.; PATON, JULIAN F. R.. Purinergic plasticity within petrosal neurons in hypertension. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 315, n. 5, p. R963-R971, NOV 2018. (15/01073-7, 13/06077-5, 16/24869-4, 13/10484-5)

CASTANIA, JACI A.; KATAYAMA, PEDRO L.; BROGNARA, FERNANDA; MORAES, DAVI J. A.; SABINO, JOAO PAULO J.; SALGADO, HELIO C.. Selective denervation of the aortic and carotid baroreceptors in rats. Experimental Physiology, v. 104, n. 9, p. 1335-1342, SEP 2019. (17/05163-6, 13/10484-5, 13/20549-7, 15/18511-7)

ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.; COLOMBARI, EDUARDO; FLOR, KARINE C.; DA SILVA, MELINA P.; COSTA-SILVA, JOAO H.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.; MURPHY, DAVID; PATON, JULIAN F. R.. Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats. Experimental Physiology, v. 104, n. 9, p. 1371-1383, SEP 2019. (13/06077-5, 15/23467-7, 13/10484-5)

SPILLER, PEDRO F.; DA SILVA, MELINA P.; MORAES, DAVI J. A.. Lactate does not activate the carotid body of Wistar rat. Respiratory Physiology & Neurobiology, v. 285, MAR 2021. (16/24869-4, 18/07027-5, 13/10484-5)

MAGALHAES, KAROLYNE S.; SPILLER, PEDRO F.; DA SILVA, MELINA P.; KUNTZE, LUCIANA B.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Locus Coeruleus as a vigilance centre for active inspiration and expiration in rats. SCIENTIFIC REPORTS, v. 8, OCT 23 2018. (13/10484-5, 15/01073-7, 17/09071-9, 16/24869-4, 13/06077-5)

PIJACKA, WIOLETTA; MORAES, DAVI J. A.; RATCLIFFE, LAURA E. K.; NIGHTINGALE, ANGUS K.; HART, EMMA C.; DA SILVA, MELINA P.; MACHADO, BENEDITO H.; MCBRYDE, FIONA D.; ABDALA, ANA P.; FORD, ANTHONY P.; et al. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nature Medicine, v. 22, n. 10, p. 1151-1159, OCT 2016. (13/06077-5, 13/10484-5)

MORAES, DAVI J. A.; BONAGAMBA, LENI G. H.; DA SILVA, MELINA P.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.. Role of ventral medullary catecholaminergic neurons for respiratory modulation of sympathetic outflow in rats. SCIENTIFIC REPORTS, v. 7, DEC 4 2017. (13/06077-5, 15/01073-7, 13/10484-5)