Role of Inhibition in the Development of Respiratory Rhythmogenesis in the Zebra Finch

Despite extensive research into the role of the brainstem in respiratory rhythmogenesis, how these neural networks develop is unclear. While rodents are valuable models, their practicality for studying brainstem development in utero is limited. Thus, we aim to use an avian model that allows for unimpeded embryonic access through prenatal development. We hypothesize that GABA/glycine receptors, which pass Cl- and mediate synaptic inhibition in adults, change during development from an excitatory to inhibitory signal and play an important role in the shape of the rhythm and pattern of respiratory activity once breathing begins on embryonic day 13 (E13). To test this hypothesis, we superfused isolated brainstems from E4 thru hatching (E14) with GABA/glycine receptor agonists and antagonists, while also recording motor output from cranial nerve IX. Results show that GABAergic/glycinergic signaling contributes to excitatory drive prior to E13, at which time their role switches to inhibition. Data also suggest that inhibition is not critical for producing motor rhythms during early development, but, once breathing begins, inhibition serves to shape the pattern of ventilatory behaviors