title: Defining preBötzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits In Vivo.
abstract: 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.
authors: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors: Yan
authors: Y
authors: Cui
authors: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors: Kaiwen
authors: K
authors: Kam
authors: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors: David
authors: D
authors: Sherman
authors: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors: Wiktor A
authors: WA
authors: Janczewski
authors: Department of Physiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors: Yu
authors: Y
authors: Zheng
authors: Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: feldman@g.ucla.edu.
authors: Jack L
authors: JL
authors: Feldman
mesh_terms: D000818:Animals; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007395:Interneurons / Q000502:physiology*; D008526:Medulla Oblongata / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways; D012119:Respiration / Q000235:genetics; D012243:Rhodopsin / Q000096:biosynthesis; D013004:Somatostatin / Q000096:biosynthesis
chemical_list: C103403:Dbx1 protein, mouse; D018398:Homeodomain Proteins; D013004:Somatostatin; D012243:Rhodopsin