Evaluating the burstlet theory of inspiratory rhythm and pattern generation

Abstract

The preBötzinger complex (preBötC) generates the rhythm and rudimentary motor pattern for inspiratory breathing movements. Here, we test “burstlet” theory (Kam et al., 2013a), which posits that low amplitude burstlets, subthreshold from the standpoint of inspiratory bursts, reflect the fundamental oscillator of the preBötC. 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 and Feldman in neonatal mouse slice preparations: field recordings from preBötC 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 preBötC neurons suggest that burstlets involve inconstant subsets of rhythmogenic interneurons. We conclude that discrete rhythm-and pattern-generating mechanisms coexist in the preBötC and that burstlets reflect its fundamental rhythmogenic nature.