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

Summary Normal breathing in rodents requires activity of glutamatergic Dbx1-derived (Dbx1 + ) preBotzinger Complex (preBotC) 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 preBotC 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 preBotC 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 preBotC or by local viral infection limiting ChR2 expression to preBotC SST + neurons. We conclude that: (1) preinspiratory preBotC Dbx1 + neurons are rhythmogenic, (2) inspiratory preBotC Dbx1 + and SST + neurons primarily act to pattern respiratory motor output, and (3) SST + -neuron-mediated pathways and postsynaptic inhibition within preBotC modulate breathing pattern.