Variability of AMPA and NMDA receptor mediated responses in CA1 pyramidal cells of young rats

The relative variability of excitatory postsynaptic currents (EPSCs) was studied using whole cell recording in CA1 pyramidal cells of hippocampal slices from 2 to 3-week-old rats. EPSCs were evoked by stimulating the Schaffer collateral-commissural pathway and recorded at holding potentials of -75, -30 or +40 mV. The recordings were either isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptor mediated EPSCs, or composite ones. EPSC variability was quantified by coefficient of variation (CV). The inverse variability expressed as 1/CV2 was employed in comparisons. Using early (5-15 ms) and late (40-100 ms) measurements to estimate the AMPA and NMDA components of composite EPSCs showed no difference in the variability of the two components. Comparing isolated AMPA EPSCs at -75 mV with NMDA EPSCs at -30 mV also failed to reveal a difference. However, in accord with previous studies by others, NMDA EPSCs recorded at +40 mV were less variable than AMPA EPSCs at -75 mV, the ratio of 1/CV2 for NMDA vs. AMPA being around 1.7. A comparison between isolated AMPA EPSCs revealed a similar pattern of dependency of CV on membrane potential, the EPSCs at +40 mV being less variable than those at -30 or -75 mV (1/CV2 ratios of 1.5-1.6). In conclusion, our results did not demonstrate any inherent difference in CV between AMPA and NMDA receptor mediated EPSCs and the observed differences in CV could be accounted for by a dependency on membrane potential, the mechanism of which remains to be resolved. The present results have implications for the interpretation of CV changes as observed, for instance, during synaptic plasticity.