The rhythm generating network for breathing must continuously adjust to changing metabolic and behavioral demands. Here, we examine network-based mechanisms in the mouse preBötzinger complex using substance P, a potent excitatory modulator of breathing frequency and stability, as a tool to dissect properties that underlie dynamic breathing. We find that substance P does not alter the balance of excitation and inhibition during breaths or the duration of the resulting refractory period. Instead, recurrent excitation between breaths is enhanced such that the rate that excitation percolates through the network is increased. Based on our results, we propose a conceptual framework in which three distinct phases, the inspiratory phase, refractory phase, and percolation phase, are differentially modulated to influence breathing dynamics and stability. Unravelling mechanisms that support this dynamic control may improve our understanding of nervous system disorders that destabilize breathing, many of which are associated with changes in brainstem neuromodulatory systems.

Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P