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

Elife. 2014 Jul 15:3:e03427. doi: 10.7554/eLife.03427.

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.

Keywords: breathing; central pattern generator; preBötzinger complex; respiration; two-photon microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Gene Expression
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Hypoglossal Nerve / physiopathology*
  • Inhalation / physiology
  • Interneurons / cytology
  • Interneurons / physiology
  • Laser Therapy
  • Mice
  • Mice, Transgenic
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Patch-Clamp Techniques
  • Respiratory Center / injuries
  • Respiratory Center / pathology
  • Respiratory Center / physiopathology*
  • Respiratory Rate
  • Tissue Culture Techniques

Substances

  • Dbx1 protein, mouse
  • Homeodomain Proteins