Ethanol dual modulatory actions on spontaneous postsynaptic currents in spinal motoneurons

Recently we have shown that acute ethanol (EtOH) exposure suppresses dorsal root-evoked synaptic potentials in spinal motoneurons. To examine the synaptic mechanisms underlying the reduced excitatory activity, EtOH actions on properties of action potential-independent miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) were studied in spinal motoneurons of newborn rats. Properties of mEPSCs generated by activation of N-methyl-D-aspartate receptors (NMDARs) and non-NMDA receptors and of mIPSCs mediated by glycine and gamma-aminobutyric acid-A receptors (GlyR and GABA(A)R) were examined during acute exposure to 70 and 200 mM EtOH. In the presence of 70 mM EtOH, the frequency of NMDAR- and non-NMDAR-mediated mEPSCs decreased to 53 +/- 5 and 45 +/- 7% (means +/- SE) of control values, respectively. In contrast, the frequency of GlyR- and GABA(A)R-mediated mIPSCs increased to 138 +/- 15 and 167 +/- 23% of control, respectively. Based on the quantal theory of transmitter release, changes in the frequency of miniature currents are correlated with changes in transmitter release, suggesting that EtOH decreased presynaptic glutamate release and increased the release of both glycine and GABA. EtOH did not change the amplitude or rise and decay times of either mEPSCs or mIPSCs, indicating that the presynaptic changes were not associated with changes in the properties of postsynaptic receptors/channels. Acute exposure to 200 mM EtOH increased mIPSC frequency two- to threefold, significantly higher than the increase induced by 70 mM EtOH. However, the decrease in mEPSC frequency was similar to that observed in 70 mM EtOH. Those findings implied that the regulatory effect of EtOH on glycine and GABA release was dose-dependent. Exposure to the higher EtOH concentration had opposite actions on mEPSC and mIPSC amplitudes: it attenuated the amplitude of NMDAR- and non-NMDAR-mediated mEPSCs to ~80% of control and increased GlyR- and GABA(A)R-mediated mIPSC amplitude by ~20%. EtOH-induced changes in the amplitude of postsynaptic currents were not associated with changes in their basic kinetic properties. Our data suggested that in spinal networks of newborn rats, EtOH was more effective in modulating the release of excitatory and inhibitory neurotransmitters than changing the properties of their receptors/channels.