Excitation-inhibition balance regulates the patterning of spinal and cranial inspiratory motor outputs in rats in situ

Spinal phrenic nerve activity (PNA) drives the diaphragm but cranial hypoglossal nerve activity (HNA) also expresses synchronous activity during inspiration. Here, we investigated the effects of local disinhibition (bilateral microinjections of bicuculline) of the nucleus tractus solitarius (NTS), the pre-Botzinger complex and Botzinger complex core circuit (pre-BotC/BotC) and the Kolliker-Fuse nuclei (KFn) on the synchronization of PNA and HNA in arterially-perfused brainstem preparations of rats. To quantitatively analyze the bicuculline effects on a putatively distributed inspiratory central pattern generator (i-CPG), we quantified the phase synchronization properties between PNA and HNA. The analysis revealed that bicuculline-evoked local disinhibition significantly reduced the strength of phase synchronization between PNA and HNA at any target site. However, the emergence of desynchronized HNA following disinhibition was more prevalent after NTS or pre-BotC/BotC microinjections compared to the KFn. We conclude that the primary i-CPG is located in a distributed medullary circuit whereas pontine contributions are restricted to synaptic gating of synchronous HNA and PNA.