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Manipulating the presence of hydrogen peroxide reveals redox modulation of rhythmogenesis originating from the in vitro pre‐Bötzinger complex.

The neuronal network within the pre‐Bötzinger complex (pre‐BötC) reconfigures itself to produce several patterns reflected in in vivo respiratory behaviors observed during changes in the oxygen environment. This study tests the hypothesis that changes in redox state surrounding the pre‐BötC has a role in network reconfiguration. Electrophysiological recordings were made in the pre‐BotC or hypoglossal nucleus of brainstem slices (~600um thick). Manipulating redox state with hydrogen peroxide (H2O2, 2.2mM) produced a depression followed augmentation in population burst frequency while extracellular catalase supplementation (20 Units/mL) produced augmentation followed by depression. Intracellular recordings from pharmacologically isolated respiratory neurons in the pre‐BötC indicate that modulating redox state, by altering the presence of H2O2, evokes changes in steady state membrane potential. Moreover, the effects on population burst frequency caused by H2O2 and catalase were also observed in the respiratory rhythm of the hypoglossal nucleus with the brainstem slice. These findings suggest that manipulating redox state of the pre‐BötC can influence inspiratory motor outflow. Our data indicate the redox state can act as a modulator of neuronal activity involved with respiratory drive. Supported Grant Number: T32HL007237 from the National Heart, Lung, and Blood Institute.