GABAAergic and Glycinergic Inhibition in the Phrenic Nucleus Organizes and Couples Fast Oscillations in Motor Output

Abstract

One of the characteristics of respiratory motor output is the presence of fast synchronous oscillations, at rates far exceeding the basic breathing rhythm, within a given functional population. However, the mechanisms responsible for organizing phrenic output into two dominant bands in vivo, medium (MFO)- and high (HFO)-frequency oscillations, have yet to be elucidated. We hypothesize that GABAAergic and glycinergic inhibition within the phrenic motor nucleus underlies the specific organization of these oscillations. To test this, the phrenic nuclei (C4) of 14 unanesthetized, decerebrate adult male Sprague-Dawley rats were microinjected unilaterally with either 4 mM strychnine ( n = 7) or GABAzine ( n = 7) to block glycine or GABAA receptors, respectively. Application of GABAzine caused an increase in overall phrenic amplitude during all three phases of respiration (inspiration, postinspiration, and expiration), while the increases caused by strychnine were most pronounced during postinspiration. Neither antagonist produced changes in inspiratory duration or respiratory rate. Power spectral analysis of inspiratory phrenic bursts showed that blockade of inhibition caused significant reduction in the relative power of MFO (GABAA and glycine receptors) and HFO (GABAA receptors only). In addition, analysis of the coherence between the firing of the ipsi- and contralateral phrenic nerves revealed that HFO coupling was significantly reduced by both antagonists and that of MFO was significantly reduced only by strychnine. We conclude that both GABAA and glycine receptors play critical roles in the organization of fast oscillations into MFO and HFO bands in the phrenic nerve, as well as in their bilateral coupling.