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Picardo, M. C.

Publications and source records attributed to Picardo, M. C..

2 recordsLinked to original sources

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

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.

neuroscience↗

Evaluating the burstlet theory of inspiratory rhythm and pattern generation

The preBotzinger complex (preBotC) generates the rhythm and rudimentary motor pattern for inspiratory breathing movements. Here, we test burstlet theory (Kam, Worrell, Janczewski, et al. 2013), which posits that low amplitude burstlets, subthreshold from the standpoint of inspiratory bursts, reflect the fundamental oscillator of the preBotC. In turn, a discrete suprathreshold process transforms burstlets into full amplitude inspiratory bursts that drive motor output, measurable via hypoglossal nerve (XII) discharge in vitro. We recap observations by Kam & Feldman: field recordings from preBotC demonstrate bursts and concurrent XII motor output intermingled with lower amplitude burstlets that do not produce XII motor output. Manipulations of excitability affect the relative prevalence of bursts and burstlets and modulate their frequency. Whole-cell and photonic recordings of preBotC neurons suggest that burstlets involve inconstant subsets of rhythmogenic interneurons. We conclude that discrete rhythm- and pattern-generating mechanisms coexist in the preBotC and that burstlets reflect its fundamental rhythmogenic nature.

neuroscience↗