Breathing matters! The sites, cells, and ion channels that underlie respiration

Breathing behavior is important and interesting. Breathing supports us physiologically, and its control and modulation underlie important cultural practices like singing, athletic performance, and mind-body practices (e.g., meditation). Breathing begins in the brain with an underlying neural rhythm and motor output pattern. Respiratory rhythm emanates from a brainstem site called the preBötzinger complex (preBötC) whose core microcircuit consists of Dbx1-derived excitatory interneurons. In those core Dbx1 neurons, the rhythmogenic mechanism depends on excitatory synaptic interactions, whose collective activity creates inhale-related burst output via mixed cationic TRPM4 ion channels. There are important roles for sodium channels of the SCN8A isoform, which influence development and control of excitability. In addition to helping us understand normal function, our knowledge of the preBötC and its constituent Dbx1-derived core neurons can explain the pathology of opioid drug depression of breathing and other dysfunctions of breathing. Neuroscience seeks to explain behaviors (pathologies) based on elemental building blocks of the nervous system: with breathing we are almost there.