Transcriptomes of Electrophysiologically Recorded Dbx1-derived Inspiratory Neurons of the preBötzinger Complex in Neonatal Mice

Abstract

Breathing depends on interneurons in the preBotzinger complex (preBotC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBotC neurons. In a slice model of breathing with [~]5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBotC neurons activate 100-300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300-500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3 and Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1) involved in inspiratory and sigh bursts. Surprisingly, neuropeptide receptors that influence breathing (e.g., {micro}-opioid and bombesin-like peptide receptors) were only sparsely expressed, which suggests that cognate peptides and opioid drugs exert their profound effects on a small fraction of the preBotC core. These data in the public domain help explain breathings neural origins.