Multibarrel micropipettes were used to simultaneously record unit activity and apply antagonists on individual inspiratory hypoglossal motoneurons (IHMNs) to determine the endogenous activation levels of NMDA, non-NMDA, GABA(A) and serotonin receptors responsible for the IHMN spontaneous discharge patterns in decerebrate dogs. IHMN activity is highly dependent on glutamatergic phasic and tonic drives, which are differentially mediated by the receptor subtypes. Endogenous serotonin significantly amplifies IHMN activity, while GABAergic gain modulation acts to attenuate activity. Thus, alterations in the neurotransmission of any of these systems could markedly alter neuronal output to target muscles.