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Neural mechanisms involved in expiratory rhythm generator: possible involvement of the retrotrapezoid nucleus and the parafacial region

Grant number: 10/09776-3
Support type:Research Grants - Young Investigators Grants
Duration: June 01, 2011 - May 31, 2015
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ana Carolina Thomaz Takakura
Grantee:Ana Carolina Thomaz Takakura
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):13/04393-7 - Participation of retrotrapezoid nucleus in expiratory activity induced by hypercapnia, BP.IC
12/03568-5 - Anatomic projections between retrotrapezoid nucleus and caudal ventral respiratory group, BP.MS

Abstract

The eupnoeic pattern of respiration consists of three phases: inspiration, post-inspiration (passive expiration, stage 1) and stage 2 of expiration. These studies demonstrated that, during respiration, phasic discharges are generated within the ventral respiratory column without the need for peripheral feedback, involving a neuronal network co-ordinated by synaptic interactions (Smith and cols., 1991) that was called ventral respiratory column. Moreover the neural mechanisms for respiratory control are carefully organized by a complex neuron system localized into the medulla oblongata. This system is highly sensitive to CO2 and maintains the CO2 and O2 in the blood into physiological level, controlling the ventilation cycle by cycle. During breathing at rest, air is expired passively by recoil forces. Augmenting expiratory activity during the second phase of expiration (E2) is always present in the brainstem during eupnoea. An expressed phasic expiratory activity in this motor outflow is observed only during increased ventilatory demand such as during exercise in man (Abraham and cols., 2002), hipercapnia or hypoxia in the cat (Fregosi and Bartlett, 1988, Fregosi, 1994, Iizuka and Fregosi, 2007). The origins and mechanisms of generation of this late expiratory activity remain poorly understood and several currently proposed concepts appear controversial. This question constitutes in one of the aims of this project. Recent evidences suggest the involvement of chemosensitive neurons of the retrotrapezoid nucleus (RTN) in the control of expiratory activity of premotor neurons of the caudal ventral respiratory group. In this way, it is important to investigate a real connection between RTN and the caudal ventral respiratory group neurons and, if it really exists, what are the physiological conditions in which such pathway emerges. In this study, we will use anatomical and electrophysiological approaches to investigate the existence of a projection from RTN to caudal ventral respiratory group neurons and the phenotype of the neurotransmitters involved in this projection. We also will study the involvement of the RTN neurons on the activation of caudal ventral respiratory group neurons. (AU)

Scientific publications (18)
(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)
SILVA, TALITA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Acute hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the C1 region. Experimental Neurology, v. 285, n. A, p. 1-11, NOV 2016. Web of Science Citations: 9.
SILVA, JOSIANE N.; LUCENA, ELVIS V.; SILVA, TALITA M.; DAMASCENO, ROSELIA S.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. INHIBITION OF THE PONTINE KOLLIKER-FUSE NUCLEUS REDUCES GENIOGLOSSAL ACTIVITY ELICITED BY STIMULATION OF THE RETROTRAPEZOID CHEMORECEPTOR NEURONS. Neuroscience, v. 328, p. 9-21, JUL 22 2016. Web of Science Citations: 8.
BARNA, B. F.; TAKAKURA, A. C.; MULKEY, D. K.; MOREIRA, T. S. Purinergic receptor blockade in the retrotrapezoid nucleus attenuates the respiratory chemoreflexes in awake rats. ACTA PHYSIOLOGICA, v. 217, n. 1, p. 80-93, MAY 2016. Web of Science Citations: 12.
MOREIRA, THIAGO S.; WENKER, IAN C.; SOBRINHO, CLEYTON R.; BARNA, BARBARA F.; TAKAKURA, ANA C.; MULKEY, DANIEL K. Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 5, p. 1067-1074, MAR 1 2015. Web of Science Citations: 6.
MULKEY, DANIEL K.; HAWKINS, VIRGINIA E.; HAWRYLUK, JOANNA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; TZINGOUNIS, ANASTASIOS V. Molecular underpinnings of ventral surface chemoreceptor function: focus on KCNQ channels. JOURNAL OF PHYSIOLOGY-LONDON, v. 593, n. 5, p. 1075-1081, MAR 1 2015. Web of Science Citations: 7.
HAWKINS, VIRGINIA E.; HAWRVLUK, JOANNA M.; TAKAKURA, ANA C.; TZINGOUNIS, ANASTASIOS V.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity. Journal of Neurophysiology, v. 113, n. 4, p. 1195-1205, FEB 15 2015. Web of Science Citations: 21.
DAMASCENO, ROSELIA S.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Respiratory and sympathetic chemoreflex regulation by Kolliker-Fuse neurons in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 467, n. 2, p. 231-239, FEB 2015. Web of Science Citations: 5.
SOBRINHO, CLEYTON R.; WENKER, IAN C.; POSS, ERIN M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Purinergic signalling contributes to chemoreception in the retrotrapezoid nucleus but not the nucleus of the solitary tract or medullary raphe. JOURNAL OF PHYSIOLOGY-LONDON, v. 592, n. 6, p. 1309-1323, MAR 15 2014. Web of Science Citations: 18.
BARNA, B. F.; TAKAKURA, A. C.; MOREIRA, T. S. ACUTE EXERCISE-INDUCED ACTIVATION OF PHOX2B-EXPRESSING NEURONS OF THE RETROTRAPEZOID NUCLEUS IN RATS MAY INVOLVE THE HYPOTHALAMUS. Neuroscience, v. 258, p. 355-363, JAN 31 2014. Web of Science Citations: 26.
TOTOLA, L. T.; ALVES, T. B.; TAKAKURA, A. C.; FERREIRA-NETO, H. C.; ANTUNES, V. R.; MENANI, J. V.; COLOMBARI, E.; MOREIRA, T. S. COMMISSURAL NUCLEUS OF THE SOLITARY TRACT REGULATES THE ANTIHYPERTENSIVE EFFECTS ELICITED BY MOXONIDINE. Neuroscience, v. 250, p. 80-91, OCT 10 2013. Web of Science Citations: 12.
WENKER, IAN C.; SOBRINHO, CLEYTON R.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. P2Y1 Receptors Expressed by C1 Neurons Determine Peripheral Chemoreceptor Modulation of Breathing, Sympathetic Activity, and Blood Pressure. Hypertension, v. 62, n. 2, p. 263-273, AUG 2013. Web of Science Citations: 19.
TAKAKURA, ANA C.; MOREIRA, THIAGO S.; DE PAULA, PATRICIA M.; MENANI, JOSE V.; COLOMBARI, EDUARDO. Control of breathing and blood pressure by parafacial neurons in conscious rats. Experimental Physiology, v. 98, n. 1, p. 304-315, JAN 2013. Web of Science Citations: 13.
BARNA, B. F.; TAKAKURA, A. C.; MOREIRA, T. S. PONTOMEDULLARY AND HYPOTHALAMIC DISTRIBUTION OF FOS-LIKE IMMUNOREACTIVE NEURONS AFTER ACUTE EXERCISE IN RATS. Neuroscience, v. 212, p. 120-130, JUN 14 2012. Web of Science Citations: 34.
WENKER, IAN C.; SOBRINHO, CLEYTON R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling. JOURNAL OF PHYSIOLOGY-LONDON, v. 590, n. 9, p. 2137-2150, MAY 2012. Web of Science Citations: 52.
TAXINI, C. L.; TAKAKURA, A. C.; GARGAGLIONI, L. H.; MOREIRA, T. S. CONTROL OF THE CENTRAL CHEMOREFLEX BY A5 NORADRENERGIC NEURONS IN RATS. Neuroscience, v. 199, p. 177-186, DEC 29 2011. Web of Science Citations: 18.
FAVERO, MICHELE T.; TAKAKURA, ANA C.; DE PAULA, PATRICIA M.; COLOMBARI, EDUARDO; MENANI, JOSE V.; MOREIRA, THIAGO S. Chemosensory control by commissural nucleus of the solitary tract in rats. Respiratory Physiology & Neurobiology, v. 179, n. 2-3, p. 227-234, DEC 15 2011. Web of Science Citations: 15.
TAKAKURA, ANA C.; MOREIRA, THIAGO S.; BORELLA, THAIS L.; PAULIN, RENATA F.; COLOMBARI, DEBORA S. A.; DE LUCA, JR., LAURIVAL A.; COLOMBARI, EDUARDO; MENANI, JOSE V. Central mechanisms involved in pilocarpine-induced pressor response. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 164, n. 1-2, p. 34-42, OCT 28 2011. Web of Science Citations: 4.
TAKAKURA, ANA C.; MOREIRA, THIAGO S. Contribution of excitatory amino acid receptors of the retrotrapezoid nucleus to the sympathetic chemoreflex in rats. Experimental Physiology, v. 96, n. 10, p. 989-999, OCT 2011. Web of Science Citations: 24.

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