Hypocapnic hypoxia silences the retrotrapezoid nucleus (RTN)

Tyler Basting, Peter Burke, Daniel Stornetta, Ruth Stornetta, Patrice Guyenet

Research output: Contribution to journalMeeting abstract

Abstract

Rationale and objectives: In conscious mammals, hypoxia produces respiratory alkalosis which is assumed to silence central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia changes the activity of the RTN, a likely CRC and chemoreflex integrator.
Methods: RTN and nearby C1 neurons were bilaterally transduced with archaerhodopsin using a lentiviral vector (PRSx8-ArchT-EYFP-LVV). We first showed that RTN neurons were silenced by green light in anesthetized rats. We then recorded the effect of RTN inhibition (10s) on breathing (fR, VT), BP, EEG and neck EMG in conscious rats exposed to normoxia, hypocapnic hypoxia (12 or 15% O2), isocapnic hypoxia (12% O2 + 3% CO2) or hypoxia in presence of acetazolamide (ACTZ). Arterial PO2, PCO2, pH and HCO3 were measured in each condition.
Results: In normoxia RTN inhibition reduced breathing equally during non-REM sleep and quiet wake and BP was unchanged. ΔfR was largest in normoxia, reduced in 15% O2, nul in 12% O2 and back to control (normoxia level) in normocapnic hypoxia.ΔVT followed the same trend. RTN inhibition caused much larger fR and VT reductions in ACTZ-treated rats. Overall the bradypnea caused by RTN inhibition was linearly correlated with pHa (p < 0.0002). Above pHa 7.5, no fR change was elicited.
Conclusions: RTN neurons regulate breathing equally during sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN is silent above pHa 7.5 and increasingly active below this value. Under hypocapnic hypoxia carotid body stimulation drives breathing via pathways that bypass RTN. ACTZ increases breathing by activating RTN. Funding: HL074011 (PGG), 5T32HL007284-38 (TMB).
Original languageEnglish
Article number1051.2
JournalFASEB Journal
Volume29
Issue number1 supplement
Publication statusPublished - Apr 2015
Externally publishedYes
EventExperimental Biology Meeting - Boston, United States
Duration: 28 Mar 20151 Apr 2015

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