Primary respiratory rhythm generator in the medulla of brainstem-spinal cord preparation from newborn rat

Abstract

It has been previously demonstrated that rhythmically firing neurons (Pre-I neurons) preceding cervical root (C 4 or C 5) inspiratory activity, localized in the rostral ventrolateral medulla (RVL), are important in the generation of the basic respiratory rhythm in brainstem-spinal cord preparations from newborn rats. We examined the effects of single and continuous electrical stimulation applied to the RVL on Pre-I and C 4 activities in these preparations. We verified that the phase of respiratory rhythm was reset when Pre-I firing was induced in both right and left RVL by single shock stimulation, whether C 4 activity appeared or not. Lower frequency and intensity of continuous pulse train stimulation in the RVL enhanced Pre-I activity, and hence C 4 activity, whereas higher frequency and intensity inhibited both. The results suggest that synchronous burst activity between the right and left Pre-I neurons must be above a certain level (in its intraburst firing rate) to trigger C 4 inspiratory activity and, therefore, that cooperation among Pre-I neurons is important for induction of rhythmic inspiratory drive. After bilateral lesions of the caudal ventrolateral medulla, Pre-I neurons retained their rhythmic activity, while C 4 activity disappeared. Present results further confirmed our hypothesis that Pre-I neurons are the primary generator of respiratory rhythm. We propose a hypothetical model of the generation of rhythmic respiratory activity.