Network Synchronization and Synchrony Propagation:Emergent Elements of Inspiration

The preBotzinger Complex (preBotC) - the kernel of breathing rhythmogenesis in mammals - is a non-canonical central pattern generator with undetermined mechanisms. We assessed preBotC network dynamics under respiratory rhythmic and nonrhythmic conditions in vitro. In each cycle under rhythmic conditions, an inspiratory burst emerges as (presumptive) preBotC rhythmogenic neurons transition from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration, triggering bursts; burst activity subsides and the cycle repeats. In a brainstem slice in nonrhythmic conditions, antagonizing GABAA receptors can initiate this periodic synchronization and consequent rhythm coincident with inducing a higher conductance state in nonrhythmogenic preBotC output neurons. Furthermore, when input synchrony onto these neurons was weak, preBotC activity failed to propagate to motor nerves. Our analyses uncover a dynamic reorganization of preBotC network activity - underpinning intricate cyclic neuronal interactions leading to network synchronization and its efficient propagation - correlated with and, we postulate, essential to, rhythmicity.