Hypoxia evokes a sequence of raphe-pontomedullary network operations for inspiratory drive amplification and gasping

• Published in: Journal of neurophysiology 2024-10, Vol.132 (4), p.1315-1329
• Main Authors: Nuding, Sarah C, Segers, Lauren S, Iceman, Kimberly E, O'Connor, Russell, Dean, Jay B, Valarezo, Pierina A, Shuman, Dale, Solomon, Irene C, Bolser, Donald C, Morris, Kendall F, Lindsey, Bruce G
• Format: Article
• Language: English
• ISSN: 0022-3077; 1522-1598; 1522-1598
• DOI: 10.1152/jn.00032.2024

Hypoxia can trigger a sequence of breathing-related behaviors, from augmentation to apneusis to apnea and gasping. Gasping is an autoresuscitative behavior that, via large tidal volumes and altered intrathoracic pressure, can enhance coronary perfusion, carotid blood flow, and sympathetic activity, and thereby coordinate cardiac and respiratory functions. We tested the hypotheses that hypoxia-evoked gasps are amplified through a disinhibitory microcircuit within the inspiratory neuron chain, and that this drive is distributed via an efference copy mechanism. This generates coordinated gasp-like discharges concurrently in other circuits of the raphe-pontomedullary respiratory network. Data were obtained from 6 decerebrate, vagotomized, neuromuscularly-blocked, and artificially ventilated adult cats. Arterial blood pressure, phrenic nerve activity, end-tidal CO , and other parameters were monitored. Hypoxia was produced by ventilation with a gas mixture of 5% O in nitrogen. Neuron spike trains were recorded at multiple pontomedullary sites simultaneously and evaluated for firing rate modulations and short-time scale correlations indicative of functional connectivity. Experimental perturbations evoked reconfiguration of raphe-pontomedullary circuits during initial augmentation, apneusis and augmented bursts, apnea, and gasping. Functional connectivity, altered firing rates, efference copy of gasp drive, and coordinated incremental blood pressure increases support a distributed brain stem network model for amplification and broadcasting of inspiratory drive during autoresuscitative gasping. Gasping begins with a reduction in inhibition by expiratory neurons and an initial loss of inspiratory drive during hypoxic apnea, and culminates in autoresuscitative efforts.