Cellular and Molecular Dissection of the Breathing Rhythm Generator

Breathing is a seemingly simple, essential behavior that rhythmically occurs about 12 times per minute. The pace and pattern of the rhythm originates in a small cluster of ~4000 neurons in the brainstem called the preBötzinger Complex (preBötC). These neurons are required for breathing, stimulation of them increases the breathing rate, and they remain cyclically active when explanted from the brain as a slice. Unlike the body's other key pacemaker, the cardiac pacemaker, the cellular and molecular basis for preBötC rhythm generation remains a mystery. In our previous work, we identified dozens of molecularly distinct preBötC neural types and, so far, in two instances have shown that molecularly distinct neural types have interesting, unexpected, and specific roles in breathing. For example, one cell type changes the pattern of breathing from a normal breath type into a sigh breath. Although we have yet to find a subset of neurons that generate the breathing rhythm, our previous studies suggest that perhaps just a small subset of preBötC neurons may be tasked to generate and control the pace of breathing. The goal of our lab is to molecularly and functionally define the different preBötC neural types that generate the breathing rhythm, dictate which breath type to take, and control the shape of the breath. We hope this work will pave the path for rationally developing precise pharmacological control of breathing which could help treat some of the most common, sleep apnea, as well as some of the most devastating, sudden infant death, diseases in medicine.