Synaptic Depression Influences Inspiratory-Expiratory Phase Transition in Dbx1 Interneurons of the preBotzinger Complex in Neonatal Mice

The brainstem preBotzinger complex (preBotC) generates the rhythm underlying inspiratory breathing movements and its core interneurons are derived from Dbx1-expressing precursors. Recurrent synaptic excitation is required to initiate inspiratory bursts, but whether excitatory synaptic mechanisms also contribute to inspiratory-expiratory phase transition is unknown. Here, we examined the role of short-term synaptic depression using a rhythmically active neonatal mouse brainstem slice preparation. We show that afferent axonal projections to Dbx1 preBotC neurons undergo activity-dependent depression and we identify a refractory period (similar to 2 s) after endogenous inspiratory bursts that precludes light-evoked bursts in channelrhodopsin-expressing Dbx1 preBotC neurons. We demonstrate that the duration of the refractory period-but neither the cycle period nor the magnitude of endogenous inspiratory bursts-is sensitive to changes in extracellular Ca2+. Further, we show that postsynaptic factors are unlikely to explain the refractory period or its modulation by Ca2+. Our findings are consistent with the hypothesis that short-term synaptic depression in Dbx1 preBotC neurons influences the inspiratory-expiratory phase transition during respiratory rhythmogenesis.