Figure 6.
Artificially manipulating the NR2A/NR2B ratio with an NR2 subunit antagonist led to θLTP/LTD shifting, suggesting that changes in the NR2A/NR2B ratio govern θLTP/LTD regulation. A, The competitive NMDAR antagonist AP-5 at 1 μm concentration did not display any marked effect on synaptic plasticity induced by the threshold protocol. AP-5 was applied before and during threshold protocol stimulation. B, Partial NR2B inhibition by the specific NR2B antagonist ifenprodil at a concentration of 0.6 μm, which inhibited NMDAR-mediated EPSCs to the same level as 1 μm AP-5 did, led to the emergence of LTD induced by the threshold protocol. C, The 1 μm AP-5 application seems to partially inhibit LTP amplitude, but this effect was not significant (1 Hz and AP-5, 117.3 ± 3.9%, n = 8, vs 1 Hz, 125.7 ± 2.8%, n = 6; p > 0.05, ANOVA post hoc LSD test). D, Comparison of EPSCs after 1 Hz LPS alone with EPSCs after 1 Hz LPS combined with partial NR2B blockade. The 1 Hz LPS led to the emergence of LTP produced with the threshold protocol. In contrast, after both 1 Hz LPS and subsequent 0.6 μm ifenprodil treatment, the threshold protocol failed to induce any persistent change. These data suggest that changes in NR2B contribute to subsequent metaplasticity. E, Summary graphs showing normalized EPSCs induced by the threshold protocol under various treatments including 1 Hz PS (1 Hz), 1 Hz PSs plus ifenprodil treatment (1 Hz & ifen.), 1 Hz PSs plus AP-5 treatment (1 Hz & AP-5), AP-5 treatment (AP-5), ifenprodil treatment, and no-priming control. F, Summary graphs showing changes in NR2A/NR2B ratios under various treatments. *p < 0.05; **p < 0.01; ***p < 0.001; ANOVA post hoc LSD test versus control. Norm., Normalized; con., control; ifen., ifenprodil.