Contribution of synaptic inhibition to the control of inspiratory hypoglossal motoneuronal (IHMN) activity in vivo

Abstract

We examine the role of endogenous γ‐aminobutyric acid (GABA)ergic and glycinergic inputs on IHMN discharge activity in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The GABAA receptor antagonist bicuculline (BIC) (200 μM), the GABAA receptor antagonist picrotoxin (PIC) (5 mM), or the glycine receptor antagonist strychnine (STR) (200 μM) was picoejected onto extracellularly‐recorded single IHMNs using multibarrel micropipettes at increasing dose‐rates until no further change in neuronal discharge frequency was observed. Presence of GABAA and glycine receptors and effectiveness of the antagonist doses were confirmed by picoejection of GABA (2 mM) or glycine (2mM) with subsequent block by the respective antagonists. At maximally effective BIC dose‐rates, the peak frequency of 20 IHMNs increased by 29 ± 30%. BIC also increased the slope of the control inspiratory phase discharge pattern by 25 ± 28%. Neither PIC (n=17, 5 ± 19%), nor STR (n =24, 3 ± 15%) had a significant effect on discharge activity. These data suggest that the basal activity of IHMNs is attenuated by a BIC‐sensitive tonic GABAergic inhibition, but phasic GABAergic inhibition and glycine receptors, although present, are not involved in controlling the activity of these neurons. Support: VA Medical Research Funds & NIH R01 GM59234.