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

Abstract

Breathing depends on interneurons in the preBötzinger complex (preBötC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBötC neurons. In a slice model of breathing with ~5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBötC 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., μ-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 preBötC core. These data in the public domain help explain the neural origins of breathing.

Putting the theory into ‘burstlet theory’ with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex

“…In the preBötC, opioids affect neuronal dynamics by binding to the μ-opioid receptor (μOR). The exact number of preBötC neurons expressing μOR is unclear; however, the number appears to be small, with estimates ranging from 8% to 50% ( Bachmutsky et al, 2020 ; Baertsch et al, 2021 ; Kallurkar et al, 2021 ). Additionally, μOR is likely to be selectively expressed on neurons involved in rhythm generation, given that opioid application in the preBötC primarily impacts burst frequency rather than amplitude ( Sun et al, 2019 ; Baertsch et al, 2021 ).…”