NR2A- and NR2B-containing NMDARs co-exist in synapses of CA1 pyramidal cells. The use of NMDAR antagonists recently ascribed selective roles to these NMDAR populations in different forms of synaptic plasticity (Liu et al., 2004; Massey et al., 2004), which conflicts with genetic approaches (Tang et al., 1999; Wong et al., 2002) and with our own results (Berberich et al., 2005). New experiments, using a NR2A-preferring and/or a NR2B-specific antagonist in hippocampal slices of P28 wild-type mice, provide evidence that NR2A- and NR2B-containing NMDARs cooperate during tetanic stimulation to induce maximal LTP. In contrast, either NR2A- or NR2B-containing NMDARs are sufficient to induce maximal LTP by low frequency pairing. This view is challenged by the fact that NR2-containing NMDARs may include the heterodimeric NR1/NR2A and NR1/NR2B as well as the heterotrimeric NR1/NR2A/NR2B receptors. To consider the possibility that functionally distinct heterotrimeric receptor assemblies form, we examined the deactivation and the peak Po of synaptic NMDA receptors during postnatal development while the NR2A/NR2B ratio increases (P14 and P28). Our results show a more pronounced developmental regulation of peak Po than of deactivation, and the additional use of subtype-preferring NMDAR antagonists suggests an increasing contribution of heterotrimeric NR1/NR2A/NR2B receptors.