NMDA receptors (NMDARs) are fundamental to learning and memory. NMDARs are heterotetrameric complexes composed of two NR1 and two NR2 subunits (NR2A-D) subunits. Neurons in the postnatal hippocampus express NR2A and NR2B, leading to the formation of diheteromeric NR1/NR2A and NR1/NR2B as well as triheteromeric NR1/NR2A/NR2B receptors. Despite compelling evidence for triheteromeric NMDARs, the functional role of these receptos in synapses is unknown.

Here, we evoked synaptic NMDA currents (NMDA EPSCs) in mouse hippocampal CA1 neurons at ?40 under physiological conditions (1 mM Mg2+) at P14, P28 and P42, and examined the peak open probability (peak Po) of synaptic NMDARs. Our results show a pronounced developmental decrease in peak Po which is a consequence of the increasing NR2A expression from P14 to P28 and is likely because of triheteromeric NR1/NR2A/NR2B receptors. The analyses of the peak, charge and deactivation of NMDA EPSCs at ?40 mV and +40 mV suggest that the three hippocampal NMDAR subtypes contribute equally to the peak of the NMDA EPSCs at both potentials. However, NMDAR-mediated charge transfer appears to be mediated by different NMDAR subtypes at ?40 mV and +40 mV. We are currently investigating the functional role of di- and triheteromeric NMDARs for bidirectional synaptic plasticity. Supported by DFG 1064/5