Oxygen sensitivity of rhythmogenesis originating from the preBötzinger complex is not a fixed property

Abstract

The role of neuronal O2 sensitivity in the preBötzinger complex (preBötC) is best demonstrated by network reconfiguration from fictive eupnea to gasping during hypoxic exposure. Here we demonstrate that the preBötC responds to relative rather than absolute changes in O2, and that the pattern of O2 exposure (sustained versus intermittent) can alter the network response to neuromodulators. Experiments employing either sustained or intermittent exposure to 0.50 or 0.95ATA O2 were conducted in the preBötC isolated in neonatal brainstem slices. Tissue O2 profiles demonstrate that neither 0.50 nor 0.95 ATA O2 produce anoxic conditions. Extracellular recordings reveal that preconditioning at 0.95 ATA O2 (10min) followed by exposure to sustained 0.50 ATA O2 leads to network reconfiguration similar to the transition from fictive eupnea to gasping. In contrast, slices maintained only in 0.50 ATA O2 possessed stable rhythms similar to fictive eupnea. Moreover, the state of oxygenation also alters the responsiveness to neuromodulation. Antagonism of 5‐HT2A receptors disrupts the rhythm at 0.50 ATA O2 when preconditioned with 0.95ATA O2 but not the rhythm maintained only in 0.50 ATA O2. While norepinephrine stabilizes rhythmogenesis following sustained exposure low levels of O2, following intermittent exposure, norepinephrine destabilizes network activity. These findings demonstrate that both the pattern and history of O2 exposure impact neuromodulation and rhythmogenesis in the preBötC. These forms of plasticity have clinical implications in the context of sleep apnea and re‐oxygenation.