Different roles for inhibition in the rhythm-generating respiratory network.

Unraveling the interplay of excitation and inhibition within rhythm-generating networks remains a fundamental issue in neuroscience. We use a biophysical model to investigate the different roles of local and long-range inhibition in the respiratory network, a key component of which is the pre-Botzinger complex inspiratory microcircuit. Increasing inhibition within the microcircuit results in a limited number of out-of-phase neurons before rhythmicity and synchrony degenerate. Thus unstructured local inhibition is destabilizing and cannot support the generation of more than one rhythm. A two-phase rhythm requires restructuring the network into two microcircuits coupled by lon-grange inhibition in the manner of a half-center. In this context, inhibition leads to greater stability of the two out-of-phase rhythms. We support our computational results with in vitro recordings from mouse pre-Botzinger complex. Partial excitation block leads to increased rhythmic variability, but this recovers after blockade of inhibition. Our results support the idea that local inhibition in the pre-Botzinger complex is present to allow for descending control of synchrony or robustness to adverse conditions like hypoxia. We conclude that the balance of inhibition and excitation determines the stability of rhythmogenesis, but with opposite roles within and between areas. These different inhibitory roles may apply to a variety of rhythmic behaviors that emerge in widespread pattern-generating circuits of the nervous system. NEW & NOTEWORTHY The roles of inhibition within the pre-Botzinger complex (preBotC) are a matter of debate. Using a combination of modeling and experiment, we demonstrate that inhibition affects synchrony, period variability, and overall frequency of the preBotC and coupled rhythmogenic networks. This work expands our understanding of ubiquitous motor and cognitive oscillatory networks.