Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis

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dc.contributor.author Basting, Tyler M.
dc.contributor.author Burke, Peter G. R.
dc.contributor.author Kanbar, Roy
dc.contributor.author Viar, Kenneth E.
dc.contributor.author Stornetta, Daniel S.
dc.contributor.author Stornetta, Ruth L.
dc.contributor.author Guyenet, Patrice G.
dc.date.accessioned 2016-10-11T10:01:39Z
dc.date.available 2016-10-11T10:01:39Z
dc.date.copyright 2015 en_US
dc.date.issued 2016-10-11
dc.identifier.issn 0270-6474 en_US
dc.identifier.uri http://hdl.handle.net/10725/4564
dc.description.abstract In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (ΔfR) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔVT) followed the same trend. The effect of hypoxia on ΔfR was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). ΔfR was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN. en_US
dc.language.iso en en_US
dc.title Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOP en_US
dc.author.idnumber 201005298 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of Neuroscience en_US
dc.journal.volume 35 en_US
dc.journal.issue 2 en_US
dc.article.pages 527-543 en_US
dc.keywords Archaerhodopsin en_US
dc.keywords Chemoreflex en_US
dc.keywords Medulla oblongata en_US
dc.keywords Optogenetics en_US
dc.keywords Phox2b en_US
dc.keywords Ventrolateral medulla en_US
dc.identifier.doi http://dx.doi.org/10.1523/JNEUROSCI.2923-14.2015 en_US
dc.identifier.ctation Basting, T. M., Burke, P. G., Kanbar, R., Viar, K. E., Stornetta, D. S., Stornetta, R. L., & Guyenet, P. G. (2015). Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis. The Journal of Neuroscience, 35(2), 527-543. en_US
dc.author.email roy.kanbar@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://www.jneurosci.org/content/35/2/527?utm_source=TrendMD&utm_medium=cpc&utm_campaign=JNeurosci_TrendMD_1 en_US

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