Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats

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dc.contributor.author Kanbar, Roy
dc.contributor.author Stornetta, Ruth L.
dc.contributor.author Cash, Devin R.
dc.contributor.author Lewis, Stephen J.
dc.contributor.author Guyenet, Patrice G.
dc.date.accessioned 2016-10-10T11:08:58Z
dc.date.available 2016-10-10T11:08:58Z
dc.date.copyright 2010 en_US
dc.date.issued 2016-10-10
dc.identifier.issn 1073-449X en_US
dc.identifier.uri http://hdl.handle.net/10725/4548
dc.description.abstract Rationale: Hypoventilation is typically treated with positive pressure ventilation or, in extreme cases, by phrenic nerve stimulation. This preclinical study explores whether direct stimulation of central chemoreceptors could be used as an alternative method to stimulate breathing. Objectives: To determine whether activation of the retrotrapezoid nucleus (RTN), which is located in the rostral ventrolateral medulla (RVLM), stimulates breathing with appropriate selectivity. Methods: A lentivirus was used to induce expression of the photoactivatable cationic channel channelrhodopsin-2 (ChR2) by RVLM Phox2b-containing neurons, a population that consists of central chemoreceptors (the ccRTN neurons) and blood pressure (BP)-regulating neurons (the C1 cells). The transfected neurons were activated with pulses of laser light. Respiratory effects were measured by plethysmography or diaphragmatic EMG recording and cardiovascular effects by monitoring BP, renal sympathetic nerve discharge, and the baroreflex. Measurements and Main Results: The RVLM contained 600 to 900 ChR2-transfected neurons (63% C1, 37% ccRTN). RVLM photostimulation significantly increased breathing rate (+42%), tidal volume (21%), minute volume (68%), and peak expiratory flow (48%). Photostimulation increased diaphragm EMG amplitude (19%) and frequency (21%). Photostimulation increased BP (4 mmHg) and renal sympathetic nerve discharge (43%) while decreasing heart rate (15 bpm). Conclusions: Photostimulation of ChR2-transfected RVLM Phox2b neurons produces a vigorous stimulation of breathing accompanied by a small sympathetically mediated increase in BP. These results demonstrate that breathing can be relatively selectively activated in resting unanesthetized mammals via optogenetic manipulation of RVLM neurons presumed to be central chemoreceptors. This methodology could perhaps be used in the future to enhance respiration in humans. en_US
dc.language.iso en en_US
dc.title Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats 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 American Journal of Respiratory and Critical Care Medicine en_US
dc.journal.volume 182 en_US
dc.journal.issue 9 en_US
dc.article.pages 1184-1194 en_US
dc.keywords Medulla oblongata en_US
dc.keywords Retrotrapezoid nucleus en_US
dc.keywords Breathing en_US
dc.keywords Chemoreceptors en_US
dc.keywords Optogenetics en_US
dc.identifier.doi http://dx.doi.org/10.1164/rccm.201001-0047OC en_US
dc.identifier.ctation Kanbar, R., Stornetta, R. L., Cash, D. R., Lewis, S. J., & Guyenet, P. G. (2010). Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats. American journal of respiratory and critical care medicine, 182(9), 1184-1194. 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 http://www.atsjournals.org/doi/abs/10.1164/rccm.201001-0047OC#.V_t0duB97cs en_US
dc.orcid.id https://orcid.org/0000-0001-5450-6443 en_US

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