Emergent Elements of Inspiratory Rhythmogenesis: Network Synchronization and Synchrony Propagation

We assessed the mechanism of mammalian breathing rhythmogenesis in the preBotzinger complex (preBotC) in vitro, where experimental tests remain inconsistent with hypotheses of canonical rhythmogenic cellular or synaptic mechanisms, i.e., pacemaker neurons or inhibition. Under rhythmic conditions, in each cycle, an inspiratory burst emerges as (presumptive) preBotC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration (for similar to 50-500 ms), which can trigger inspiratory bursts that propagate to motoneurons. In nonrhythmic conditions, antagonizing GABA(A) receptors can initiate this synchronization while inducing a higher conductance state in nonrhythmogenic preBotC output neurons. Our analyses uncover salient features of preBotC network dynamics where inspiratory bursts arise when and only when the preBotC rhythmogenic subpopulation strongly synchronizes to drive output neurons. Furthermore, downstream propagation of preBotC network activity, ultimately to motoneurons, is dependent on the strength of input synchrony onto preBotC output neurons exemplifying synchronous propagation of network activity.