Anatomy Seminar: Illuminating The Neural Microcircuits Controlling Breathing

Breathing is a vital rhythmic motor behavior controlled by brainstem microcircuits. One such microcircuit, the preBötzinger Complex (preBötC), produces rhythmic population activity that drives inspiratory motor output. Despite the apparent simplicity of its function, the mechanisms generating inspiratory rhythmic activity in preBötC are unknown. We found that rhythmic preBötC activity consisted of two separable components: small amplitude burstlets, which we hypothesize are rhythmogenic, and larger inspiratory bursts, which initiate a pattern-generating process essential for motor output. Consistent with the burstlet hypothesis, neuromodulators that affect breathing frequency, such as opioids, also affected burstlet frequency in medullary slices from neonatal mice. To characterize preBötC network properties that contribute to rhythmogenesis, we utilized an advanced optical technique, holographic photostimulation, which allows patterning of light to excite multiple regions simultaneously. Holographic photostimulation of just 4-9 preBötzinger Complex inspiratory neurons, <1% of the population, was capable of producing inspiratory-related bursts. Surprisingly, this evoked motor output occurred after a delay of ~250 ms, comparable to, and perhaps congruent with, the duration of burstlet activity. Our findings reveal distinct rhythm- and pattern-generating functions in preBötC and place critical and novel boundary conditions on the neural microcircuit controlling breathing.