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

Hypoxia can trigger a sequence of breathing-related behaviors, from tachypnea to apneusis to apnea and gasping, 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 hypothesis that hypoxia-evoked gasps are amplified through a disinhibitory microcircuit within the inspiratory neuron chain and a distributed efference copy mechanism that 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 CO2, and other parameters were monitored. Hypoxia was produced by ventilation with a gas mixture of 5% O2 in nitrogen (N2). 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 tachypnea, apneusis and augmented bursts, apnea, and gasping. The functional connectivity, altered firing rates, efference copy of gasp drive, and coordinated step increments in blood pressure reported here support a distributed brain stem network model for amplification and broadcasting of inspiratory drive during autoresuscitative gasping that begins with a reduction in inhibition by expiratory neurons and an initial loss of inspiratory drive during hypoxic apnea.