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Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity

Grant number: 15/23376-1
Support type:Research Projects - Thematic Grants
Duration: February 01, 2017 - January 31, 2022
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Thiago dos Santos Moreira
Grantee:Thiago dos Santos Moreira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Co-Principal Investigators:Ana Carolina Thomaz Takakura
Assoc. researchers:Norberto Garcia Cairasco
Associated grant(s):17/12072-7 - Multi-user equipment approved in grant 2015/23376-1: Zeiss AxioImager microscope with fluorescence, light/dark field, digital camera and hardware and system analysis, AP.EMU
Associated scholarship(s):18/13707-9 - Involvement of the chemosensitive neurons in the retrotrapezoid nucleus for the control of postinspiratory activity, BP.DR
18/13704-0 - Study of the influence of omega-3 in the respiratory changes observed in a model of Parkinson's Disease induced by bilateral injection of 6-hydroxy-dopamine in CPU, BP.IC
17/08696-5 - Purinergic signalling within the retrotrapezoid nucleus region: role of breathing control in the temporal lobe epilepsy model, BP.PD
17/10242-2 - Role of OLIG3 transcription factor on ventilatory responses to hypoxia and hypercapnia, BP.IC
17/01380-2 - Pedunculo pontine tegmental nucleus and brainstem respiratory interactions in breathing, BP.DD

Abstract

Breathing automaticity and chemoreception are inseparable neural processes. The retrotrapezoid nucleus (RTN), a group of glutamatergic neurons that express the transcription factor Phox2b, may be a crucial nodal point through which breathing automaticity is regulated to maintain CO2 constant. Additional evidence that RTN neurons have central respiratory chemoreceptor properties is presented, but this is only one of many factors that determine their activity. The RTN is also regulated by powerful inputs from the carotid bodies and, at least in the adult, by many other synaptic inputs. It is also established that RTN neurons may control the activity of the downstream central respiratory pattern generator. Specifically, RTN neurons (a) innervate the entire ventral respiratory column and (b) control both inspiration and expiration. Based on the information above, this project will intend to analyze the role of RTN chemoreceptors neurons in the control of breathing under physiological, pathological and during development in mammals. (AU)

Articles published in Agência FAPESP about the research grant
Studies explain the mechanisms that govern breathing 

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)
OLIVEIRA, LUIZ M.; OLIVEIRA, MARIA A.; MORIYA, HENRIQUE T.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Respiratory disturbances in a mouse model of Parkinson's disease. Experimental Physiology, v. 104, n. 5, p. 729-739, MAY 1 2019. Web of Science Citations: 1.
CZEISLER, CATHERINE M.; SILVA, TALITA M.; FAIR, SUMMER R.; LIU, JILLIAN; TUPAL, SRINIVASAN; KAYA, BEHIYE; COWGILL, AARON; MAHAJAN, SALIL; SILVA, PHELIPE E.; WANG, YANGYANG; BLISSETT, ANGELA R.; GOKSEL, MUSTAFA; BORNIGER, JEREMY C.; ZHANG, NING; FERNANDES-JUNIOR, SILVIO A.; CATACUTAN, FAY; ALVES, MICHELE J.; NELSON, RANDY J.; SUNDARESEAN, VISHNU; REKLING, JENS; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; OTERO, JOSE J. The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 8, p. 2225-2251, APR 15 2019. Web of Science Citations: 0.
LIMA, JANAYNA D.; SOBRINHO, CLEYTON R.; FALQUETTO, BARBARA; SANTOS, LEONARDO K.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Cholinergic neurons in the pedunculopontine tegmental nucleus modulate breathing in rats by direct projections to the retrotrapezoid nucleus. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 7, p. 1919-1934, APR 2019. Web of Science Citations: 0.
ANDRADE, DAVID C.; TOLEDO, CAMILO; DIAZ, HUGO S.; LUCERO, CLAUDIA; ARCE-ALVAREZ, ALEXIS; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.; SCHULTZ, HAROLD D.; MARCUS, NOAH J.; ALCAYAGA, JULIO; DEL RIO, RODRIGO. Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure. Clinical Science, v. 133, n. 3, p. 393-405, FEB 14 2019. Web of Science Citations: 0.
MOREIRA, THIAGO S.; ANTUNES, VAGNER R.; FALQUETTO, BARBARA; MARINA, NEPHTALI. Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat. Journal of Hypertension, v. 36, n. 12, p. 2444-2452, DEC 2018. Web of Science Citations: 0.
JAMES, S. D.; HAWKINS, V. E.; FALQUETTO, B.; RUSKIN, D. N.; MASINO, S. A.; MOREIRA, T. S.; OLSEN, M. L.; MULKEY, D. K. Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus. ENEURO, v. 5, n. 6 NOV-DEC 2018. Web of Science Citations: 0.
MALHEIROS-LIMA, MILENE R.; TOTOLA, LEONARDO T.; LANA, MARLOUS V. G.; STRAUSS, BRYAN E.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. Breathing responses produced by optogenetic stimulation of adrenergic C1 neurons are dependent on the connection with preBotzinger complex in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 470, n. 11, p. 1659-1672, NOV 2018. Web of Science Citations: 0.
OLIVEIRA, LUIZ M.; FALQUETTO, BARBARA; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Orexinergic neurons are involved in the chemosensory control of breathing during the dark phase in a Parkinson's disease model. Experimental Neurology, v. 309, p. 107-118, NOV 2018. Web of Science Citations: 0.
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. Web of Science Citations: 1.
FERNANDES-JUNIOR, SILVIO A.; CARVALHO, KARIN S.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Correlation between neuroanatomical and functional respiratory changes observed in an experimental model of Parkinson's disease. Experimental Physiology, v. 103, n. 10, p. 1377-1389, OCT 1 2018. Web of Science Citations: 4.
FALQUETTO, BARBARA; OLIVEIRA, LUIZ M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Inhibition of the hypercapnic ventilatory response by adenosine in the retrotrapezoid nucleus in awake rats. Neuropharmacology, v. 138, p. 47-56, AUG 2018. Web of Science Citations: 1.
SILVA, TALITA M.; CHAAR, LAIALI J.; SILVA, REINALDO C.; TAKAKURA, ANA C.; CAMARA, NIELS O.; ANTUNES, VAGNER R.; MOREIRA, THIAGO S. Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia. Experimental Physiology, v. 103, n. 6, p. 884-895, JUN 1 2018. Web of Science Citations: 3.
LIMA, JULIANA C.; OLIVEIRA, LUIZ M.; BOTELHO, MARINA T.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson's disease. Experimental Neurology, v. 302, p. 46-56, APR 2018. Web of Science Citations: 5.
OLIVEIRA, LUIZ M.; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Raphe Pallidus is Not Important to Central Chemoreception in a Rat Model of Parkinson's Disease. Neuroscience, v. 369, p. 350-362, JAN 15 2018. Web of Science Citations: 3.
SOBRINHO, CLEYTON R.; GONCALVES, CHRISTOPHER M.; TAKAKURA, ANA C.; MULKEY, DANIEL K.; MOREIRA, THIAGO S. Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing. Journal of Neurophysiology, v. 118, n. 3, p. 1690-1697, SEP 2017. Web of Science Citations: 5.
OLIVEIRA, LUIZ M.; TUPPY, MARINA; MOREIRA, THIAGO S.; TAKAKURA, ANA C. Role of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson's disease model. Experimental Neurology, v. 293, p. 172-180, JUL 2017. Web of Science Citations: 10.
MALHEIROS-LIMA, MILENE R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S. DEPLETION OF ROSTRAL VENTROLATERAL MEDULLARY CATECHOLAMINERGIC NEURONS IMPAIRS THE HYPDXIC VENTILATORY RESPONSE IN CONSCIOUS RATS. Neuroscience, v. 351, p. 1-14, MAY 20 2017. Web of Science Citations: 7.
HAWKINS, VIRGINIA E.; TAKAKURA, ANA C.; TRINH, ASHLEY; MALHEIROS-LIMA, MILENE R.; CLEARY, COLIN M.; WENKER, IAN C.; DUBREUIL, TODD; RODRIGUEZ, ELLIOT M.; NELSON, MARK T.; MOREIRA, THIAGO S.; MULKEY, DANIEL K. Purinergic regulation of vascular tone in the retrotrapezoid nucleus is specialized to support the drive to breathe. eLIFE, v. 6, APR 7 2017. Web of Science Citations: 13.

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