Developmental changes in the modulation of synaptic glycine receptors by ethanol

During postnatal motoneuron development, the glycine receptor (GlyR) alpha subunit changes from alpha2 (fetal) to alpha1 (adult). To study the effect this change has on ethanol potentiation of GlyR currents in hypoglossal mot oneurons (HMs), we placed neurons into two groups: neonate [postnatal day 1 to 3 (P1-3)], primarily expressing a2, and juvenile (P9-13), primarily exp ressing alpha1. We found that glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in neonate HMs are less sensitive to ethanol than in juveniles. Thirty millimolar ethanol increased the amplitude of ju venile mIPSCs but did not significantly change neonatal mIPSCs. However, 10 0 mM ethanol increased the amplitudes of both neonate and juvenile mIPSCs. There was a significant difference between age groups in the average ethano l-induced increase in mIPSC amplitude for 10, 30, 50, and 100 mM ethanol. I n both age groups ethanol increased the frequency of glycinergic mIPSCs, bu t there was no difference in the amount of frequency increase between age g roups. Ethanol (100 mM) also potentiated evoked IPSCs (eIPSCs) in both neon ate and juvenile HMs. As we observed for mIPSCs, 30 mM ethanol increased th e amplitude of juvenile eIPSCs, but had no significant effect on eIPSCs in neonate HMs. Ethanol also potentiated currents induced by exogenously appli ed glycine in both neonate and juvenile HMs. These results suggest that eth anol directly modulates the GlyR. To investigate possible mechanisms for th is, we analyzed the time course of mIPSCs and single-channel conductance of the GlyR in the presence and absence of ethanol. We found that ethanol did not significantly change the time course of mIPSCs. We also determined tha t ethanol did not significantly change the single-channel conductance of sy naptic GlyRs, as estimated by nonstationary noise analysis of mIPSCs. We co nclude that the adult form of the native GlyR is more sensitive to ethanol than the fetal form. Further, enhancement of GlyR currents involves mechani sms other than an increase in the single-channel conductance or factors tha t alter the decay kinetics.