Depression of Synaptic N-methyl-D-Aspartate Responses by Xenon and Nitrous Oxide

In “synapse bouton preparation” of rat hippocampal CA3 neurons, we examined how Xe and N₂O modulate N-methyl-D-aspartate (NMDA) receptor-mediated spontaneous and evoked excitatory post-synaptic currents (sEPSC_NMDA and eEPSC_NMDA). This preparation is a mechanically isolated single neuron attached with nerve endings (boutons) preserving normal physiologic function and promoting the exact evaluation of sEPSC_NMDA and eEPSC_NMDA responses without influence of extrasynaptic, glial, and other neuronal tonic currents. These sEPSCs and eEPSCs are elicited by spontaneous glutamate release from many homologous glutamatergic boutons and by focal paired-pulse electric stimulation of a single bouton, respectively. The s/eEPSC_AMPA/KA and s/eEPSC_NMDA were isolated pharmacologically by their specific antagonists. Thus, independent contributions of pre- and postsynaptic responses could also be quantified. All kinetic properties of s/eEPSC_AMPA/KA and s/eEPSC_NMDA were detected clearly. The s/eEPSC_NMDA showed smaller amplitude and slower rise and 1/e decay time constant (τ_Decay) than s/eEPSC_AMPA/KA. Xe (70%) and N₂O (70%) significantly decreased the frequency and amplitude without altering the τ_Decay of sEPSC_NMDA. They also decreased the amplitude but increased the Rf and PPR without altering the τ_Decay of the eEPSC_NMDA. These data show clearly that “synapse bouton preparation” can be an accurate model for evaluating s/eEPSC_NMDA. Such inhibitory effects of gas anesthetics are primarily due to presynaptic mechanisms. Present results may explain partially the powerful analgesic effects of Xe and N₂O.