Kevin Yackle, PhD, MD

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 several 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 and another relays the breathing signal to higher order brain centers that control arousal. This suggest that perhaps just a small subset of different preBötC neurons may be tasked to generate and control the pace of breathing or control specific aspects of the breath shape. Once these cell types are defined, we hope to characterize how they interact to create breathing behavior. We hope our work defining the key cell types and molecules for breathing will pave the path for rationally developing precise pharmacological approaches to control it. Therapies like this could help treat some of the most common as well as some of the most devastating diseases in medicine like sleep apnea and sudden infant death.

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Academic community service and committee membership:

NS NSF Mentor, Completed multiple mentorship training workshops.