Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization

Interneuronal electrical coupling via gap junctions and chemical synaptic i nhibitory transmission are known to have roles in the generation and synchr onization of activity in neuronal networks. Uncertainty exists regarding th e roles of these two modes of interneuronal communication in the central re spiratory rhythm-generating system. To assess their roles, we performed stu dies on both the neonatal mouse medullary slice and en bloc brain stem-spin al cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic ins piratory activity observed had two temporal characteristics: the basic resp iratory frequency occurring on a long time scale and the synchronous neuron al discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blo ckers, including 18 alpha -glycyrrhetinic acid, 18 beta -glycyrrhetinic aci d, and carbenoxolone, all caused a reduction in respiratory frequency. In c ontrast, peak integrated phrenic and hypoglossal inspiratory activity was n ot significantly changed by gap-junction blockade. On a short-time-scale, g ap-junction blockade increased the degree of synchronization within an insp iratory burst observed in both nerves. In contrast, opposite results were o bserved with blockade of GABA(A) and glycine receptors. We found that respi ratory frequency increased with receptor blockade, and simultaneous blockad e of both receptors consistently resulted in a reduction in short-time-scal e synchronized activity observed in phrenic and hypoglossal inspiratory bur sts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of re spiratory cycle timing and an inspiratory pattern generator that is involve d in short-time-scale synchronization. In the neonatal rodent, properties o f both components can be regulated by interneuronal communication via gap j unctions and inhibitory synaptic transmission.