Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice

Abstract

To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors. Here, we show that selective photonic destruction of Dbx1 preBötC neurons in neonatal mouse slices impairs respiratory rhythm but surprisingly also the magnitude of motor output; respiratory hypoglossal nerve discharge decreased and its frequency steadily diminished until rhythm stopped irreversibly after 85±20 (mean ± SEM) cellular ablations, which corresponds to ∼15% of the estimated population. These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations. We also establish quantitative cellular parameters that govern network viability, which may have ramifications for respiratory pathology in disease states.DOI: http://dx.doi.org/10.7554/eLife.03427.001

Robust network oscillations during mammalian respiratory rhythm generation driven by synaptic dynamics

“…Normalizing the number of lesioned neurons to the total required for complete rhythm cessation resulted in exponential increases in the CPs and variability (Fig. 2Ac), comparable to those obtained in previous physiological in vitro experiments (20,25). The proportion of lesioned neurons required to stop bursting is nevertheless higher than observed experimentally in vitro (Discussion and SI Appendix, Fig.…”

“…Network connectivity within the preBötC could influence the dynamics of population activity (49). Other preBötC-related studies have used all-to-all coupling (9) or various degrees of sparse networks (13,25) including small-world topology (7). In this study, we modeled a realistic-sized preBötC network using random connections between neurons with a distribution law that decays exponentially with the distance between neurons (Fig.…”

Defining preBötzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits In Vivo

“…Indeed, a subpopulation of Dbx1 + neurons has intrinsic membrane properties and premotoneuronal axonal projections consistent with a patterning function (Picardo et al, 2013; Revill et al, 2015; Wang et al, 2014). In SST-ChR2 mice, bilateral preBötC SPP excited inspiratory preBötC neurons (Figure 8, I SST + Glu + ).…”

“…preBötC Dbx1 + neurons are strong candidates as generators of inspiratory rhythm (Wang et al, 2014). In rhythmically active slice preparations from neonatal rodents, preBötC Dbx1 + neurons have a preinspiratory firing pattern, initiating spike activity before the onset of each inspiratory hypoglossal nerve burst, and continue to fire throughout inspiration (Picardo et al, 2013).…”

“…In rhythmically active slice preparations from neonatal rodents, preBötC Dbx1 + neurons have a preinspiratory firing pattern, initiating spike activity before the onset of each inspiratory hypoglossal nerve burst, and continue to fire throughout inspiration (Picardo et al, 2013). In vitro , a subset of Dbx1 + neurons are premotoneurons, projecting directly to motoneurons, transmitting bursts of inspiratory activity that ultimately pattern inspiratory muscle contraction (Kam et al, 2013a; Revill et al, 2015; Wang et al, 2014). SST is expressed in a subset of preBötC Dbx1 + neurons that partially overlap with neurokinin 1 receptor-positive (NK1R + ) neurons (Gray et al, 2010; Stornetta et al, 2003).…”