Neural mechanisms generating the respiratory pattern and the respiratory-sympathetic coupling in conditions of hypoxia

• Grant number: 13/17251-6
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: September 01, 2014
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Daniel Breseghello Zoccal
• Grantee: Daniel Breseghello Zoccal
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 18/04439-0 - Functional interaction between raphe and retrotrapezoid nuclei for the control of breathing pattern and hypercapnic ventilatory response in rats, BP.MS; 15/23568-8 - Inhibitory control of the active expiratory pattern in rats submitted to chronic hypoxia, BP.MS

Abstract

The resting respiratory activity is generated by the synchronized activity of a complex brainstem neural respiratory network, which contains a primary oscillator essential for respiratory rhythmicity. This respiratory oscillator is located within the ventral respiratory column and is composed by pacemaker inspiratory neurons. However, recent studies suggest the presence of a second respiratory oscillator critical for the emergence of active expiratory pattern, as observed in conditions of hypoxia or hypercapnia. This expiratory oscillator is suggested to be located rostral to the ventral respiratory column, ventral to the facial nucleus, in the parafacial respiratory group (pFRG). In addition to its important role for the generation of active expiratory pattern, studies suggest that the respiratory neurons of the pFRG also interact with the neurons involved with the generation of sympathetic activity, contributing for the excitation of sympathetic activity in conditions of hypercapnia. Thereby, it has been proposed that the respiratory neurons of the pFRG play a critical role for the coordinated control of sympathetic and respiratory activities, especially in conditions of metabolic challenges. Nevertheless, some important aspects of the role of pFRG neurons still deserve experimental verification, such as: i) the functional characteristics of the pFRG neurons (chemosensitivity, for example); ii) the synaptic conditions required for the activation of pFRG neurons (excitatory and inhibitory balance); iii) the connectivity of the pFRG neurons with other respiratory neurons, which underlie the generation of active expiratory pattern; and iv) the connectivity with sympathetic neurons, which may contribute to the increase in sympathetic activity coupled with respiratory activity. The clarification of these aspects will be important to verify the neural mechanisms underpinning the generation of active expiration and its coupling with sympathetic nervous system; as well as will contribute for the understanding of the development of cardiorespiratory adaptations induced by the exposure to chronic hypoxia - a condition commonly associated to pathophysiological conditions. Accordingly, in the present study we sought to verify novel concepts about the neural mechanisms responsible for the generation of active expiration and its coupling with sympathetic activity in healthy rats as well as in rats exposed to chronic hypoxia. To this, we will use electrophysiological techniques (nerve and neuronal recordings), immunohistochemical procedures and the experimental model of juvenile rats submitted to chronic hypoxia (10% O2) for 24 h. (AU)

Scientific publications

(19)

(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)

BARNETT, WILLIAM H.; ABDALA, ANA P.; PATON, JULIAN F. R.; RYBAK, ILYA A.; ZOCCAL, DANIEL B.; MOLKOV, YAROSLAV I.. Chemoreception and neuroplasticity in respiratory circuits. Experimental Neurology, v. 287, n. 2, SI, p. 153-164, JAN 2017. (13/17251-6)

TAXINI, CAMILA L.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.; BICEGO, KENIA C.; GARGAGLIONI, LUCIANE H.; ZOCCAL, DANIEL B.. ROLE OF A5 NORADRENERGIC NEURONS IN THE CHEMOREFLEX CONTROL OF RESPIRATORY AND SYMPATHETIC ACTIVITIES IN UNANESTHETIZED CONDITIONS. Neuroscience, v. 354, p. 146-157, JUN 23 2017. (13/06077-5, 13/17251-6)

LEMES, E. V.; AIKO, S.; ORBEM, C. B.; FORMENTIN, C.; BASSI, M.; COLOMBARI, E.; ZOCCAL, D. B.. Long-term facilitation of expiratory and sympathetic activities following acute intermittent hypoxia in rats. ACTA PHYSIOLOGICA, v. 217, n. 3, p. 254-266, JUL 2016. (09/54888-7, 13/17251-6, 14/06976-2)

LEIRAO, ISABELA P.; COLOMBARI, DEBORA S. A.; DA SILVA, GLAUBER S. F.; ZOCCAL, DANIEL B.. Lesion of Serotonergic Afferents to the Retrotrapezoid Nucleus Impairs the Tachypneic Response to Hypercapnia in Unanesthetized Animals. Neuroscience, v. 452, p. 63-77, JAN 1 2021. (18/21000-2, 13/17251-6, 18/04439-0)

KARLEN-AMARANTE, MARLUSA; ZOCCAL, DANIEL B.; MENANI, JOSE V.; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.. OFFSPRING OF OBESE DAMS PRESENT CHANGES IN RESPIRATORY AND SYMPATHETIC ACTIVITIES. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (13/17251-6, 16/23513-1)

JENKIN, SARAH E. M.; MILSOM, WILLIAM K.; ZOCCAL, DANIEL B.. THE KOLLIKER-FUSE NUCLEUS ACTS AS A TIMEKEEPER FOR LATE-EXPIRATORY ABDOMINAL ACTIVITY. Neuroscience, v. 348, p. 63-72, APR 21 2017. (13/17251-6)

BITTENCOURT-SILVA, PALOMA G.; MENEZES, MIGUEL FURTADO; MENDONCA-JUNIOR, BOLIVAL A.; KARLEN-AMARANTE, MARLUSA; ZOCCAL, DANIEL B.. Postnatal intermittent hypoxia enhances phrenic and reduces vagal upper airway motor activities in rats by epigenetic mechanisms. Experimental Physiology, v. 105, n. 1, p. 148-159, JAN 2020. (13/06077-5, 13/17251-6)

MELO, MARIANA ROSSO; VOGER, JOSHUA J.; CONNELLY, ANGELA A.; BASSI, JASPREET K.; COLOMBARI, EDUARDO; ALLEN, ANDREW M.. Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats. Neuroscience Letters, v. 787, p. 6-pg., 2022-07-30. (15/23467-7, 16/02091-1, 14/01159-6, 13/17251-6)

MENDONCA-JUNIOR, BOLIVAL A.; FERNANDES, V, MARCOS; ZOCCAL, DANIEL B.. Acute intermittent hypoxia evokes ventilatory long-term facilitation and active expiration in unanesthetized rats. Respiratory Physiology & Neurobiology, v. 294, DEC 2021. (13/17251-6, 18/21000-2)

ZOCCAL, DANIEL B.; SILVA, JOSIANE N.; BARNETT, WILLIAM H.; LEMES, EDUARDO V.; FALQUETTO, BARBARA; COLOMBARI, EDUARDO; MOLKOV, YAROSLAV I.; MOREIRA, THIAGO S.; TAKAKURA, ANA C.. Interaction between the retrotrapezoid nucleus and the parafacial respiratory group to regulate active expiration and sympathetic activity in rats. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, v. 315, n. 5, p. L891-L909, NOV 2018. (14/22406-1, 13/17251-6, 15/23376-1, 16/23281-3, 09/54888-7, 16/22069-0)

FURUYA, WERNER I.; BASSI, MIRIAN; MENANI, JOSE V.; COLOMBARI, EDUARDO; ZOCCAL, DANIEL B.; COLOMBARI, DEBORA S. A.. Modulation of hypercapnic respiratory response by cholinergic transmission in the commissural nucleus of the solitary tract. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 472, n. 1, DEC 2019. (13/22526-4, 13/17251-6)

LEMES, EDUARDO V.; COLOMBARI, EDUARDO; ZOCCAL, DANIEL B.. Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats. Journal of Applied Physiology, v. 121, n. 5, p. 1135-1144, NOV 1 2016. (09/54888-7, 13/17251-6, 14/06976-2)

SPERETTA, GUILHERME F.; LEMES, EDUARDO VIEIRA; VENDRAMINI, REGINA C.; MENANI, JOSE V.; ZOCCAL, DANIEL B.; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.; BASSI, MIRIAN. High-fat diet increases respiratory frequency and abdominal expiratory motor activity during hypercapnia. Respiratory Physiology & Neurobiology, v. 258, p. 32-39, DEC 2018. (13/17251-6, 13/13118-0)

DA SILVA, ELAINE FERNANDA; BASSI, MIRIAN; MENANI, JOSE VANDERLEI; ALMEIDA COLOMBARI, DEBORA SIMOES; ZOCCAL, DANIEL BRESEGHELLO; PEDRINO, GUSTAVO RODRIGUES; COLOMBARI, EDUARDO. Carotid bodies contribute to sympathoexcitation induced by acute salt overload. Experimental Physiology, v. 104, n. 1, p. 15-27, JAN 2019. (11/50770-1, 13/17251-6, 15/23467-7)

MELO, MARIANA ROSSO; GASPARINI, SILVIA; SPERETTA, GUILHERME F.; SILVA, ELAINE FERNANDA; PEDRINO, GUSTAVO RODRIGUES; MENANI, V, JOSE; ZOCCAL, DANIEL B.; ALMEIDA COLOMBARI, DEBORA SIMOES; COLOMBARI, EDUARDO. Importance of the commissural nucleus of the solitary tract in renovascular hypertension. HYPERTENSION RESEARCH, v. 42, n. 5, p. 587-597, MAY 2019. (14/01159-6, 13/17251-6, 15/23467-7)

BARNETT, WILLIAM H.; ABDALA, ANA P.; PATON, JULIAN F. R.; RYBAK, ILYA A.; ZOCCAL, DANIEL B.; MOLKOV, YAROSLAV I.. Chemoreception and neuroplasticity in respiratory circuits. Experimental Neurology, v. 287, p. 12-pg., 2017-01-01. (13/17251-6)

KARLEN-AMARANTE, MARLUSA; ISABELA, I. P.; KATAYAMA, PEDRO L.; COLOMBARI, EDUARDO; BITTENCOURT-SILVA, PALOMA G.; MENEZES, MIGUEL F.; ZOCCAL, D. B.. Sympathetic dysregulation induced by postnatal intermittent hypoxia. Sleep, v. N/A, p. 13-pg., 2023-03-02. (13/17251-6, 20/05045-6, 19/11196-0)

JENKIN, SARAH E. M.; MILSOM, WILLIAM K.; ZOCCAL, DANIEL B.. Inhibitory control of active expiration by the Kolliker-Fuse in rats. FASEB JOURNAL, v. 30, p. 1-pg., 2016-04-01. (13/17251-6)

LEMES, EDUARDO; ZOCCAL, DANIEL. Active expiration and sympathetic excitation during hypercapnia require glutamatergic neurotransmission in the retrotrapezoid nucleus. FASEB JOURNAL, v. 30, p. 1-pg., 2016-04-01. (13/17251-6)