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

• Published in: Neuron (Cambridge, Mass.) Mass.), 2016-08, Vol.91 (3), p.602-614
• Main Authors: Cui, Yan, Kam, Kaiwen, Sherman, David, Janczewski, Wiktor A., Zheng, Yu, Feldman, Jack L.
• Format: Article
• Language: English
• Subjects: Animals; Homeodomain Proteins - biosynthesis; Interneurons - physiology; Laboratories; Medulla Oblongata - cytology; Medulla Oblongata - physiology; Mice; Mice, Transgenic; Neural Inhibition - physiology; Neural Pathways; Neurons; Respiration - genetics; Rhodopsin - biosynthesis; Rodents; Roles; Somatostatin - biosynthesis; Transgenic animals
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2016.07.003

Normal breathing in rodents requires activity of glutamatergic Dbx1-derived (Dbx1+) preBötzinger Complex (preBötC) neurons expressing somatostatin (SST). We combined in vivo optogenetic and pharmacological perturbations to elucidate the functional roles of these neurons in breathing. In transgenic adult mice expressing channelrhodopsin (ChR2) in Dbx1+ neurons, photoresponsive preBötC neurons had preinspiratory or inspiratory firing patterns associated with excitatory effects on burst timing and pattern. In transgenic adult mice expressing ChR2 in SST+ neurons, photoresponsive preBötC neurons had inspiratory or postinspiratory firing patterns associated with excitatory responses on pattern or inhibitory responses that were largely eliminated by blocking synaptic inhibition within preBötC or by local viral infection limiting ChR2 expression to preBötC SST+ neurons. We conclude that: (1) preinspiratory preBötC Dbx1+ neurons are rhythmogenic, (2) inspiratory preBötC Dbx1+ and SST+ neurons primarily act to pattern respiratory motor output, and (3) SST+-neuron-mediated pathways and postsynaptic inhibition within preBötC modulate breathing pattern. •Preinspiratory preBötC Dbx1+ neurons are respiratory rhythmogenic•Inspiratory preBötC Dbx1+ and SST+ neurons shape motor output pattern•SST+-neuron-mediated inhibitory pathways modulate respiratory activity•Postsynaptic inhibition broadens dynamic range and stabilizes breathing pattern Cui et al. combine in vivo optogenetic and pharmacological perturbations to dissect the neural microcircuits controlling breathing and to elucidate the functional role of preBötinger Complex Dbx1+ and SST+ neurons that underlie a microcircuit model for respiratory rhythm and pattern generation.