Functional NMDARs are made up of NR1 and NR2 subunits. The latter critically determines the susceptibility of the receptor to Mg2+ block and its single-channel conductance. Receptors containing NR2A or NR2B show a higher conductance and greater sensitivity to Mg2+ block. By contrast, receptors containing NR2C or NR2D have a lower conductance and reduced Mg2+ sensitivity, such that they are more likely to open at resting membrane potentials. Previous studies in the rodent dentate gyrus provided evidence for NMDAR-mediated synaptic currents at negative membrane potentials. However, the properties of the underlying NMDA channels have not been characterized. Here, we examined NMDA single channel properties and NMDAR-mediated synaptic currents in the mouse dentate gyrus. Whole cell recording from granule cells in horizontal hippocampal slices bathed in 2 mM Mg2+ revealed prominent DNQX-resistant, APV-sensitive, slowly decaying spontaneous EPSCs at ?70 mV. Single NMDA channel currents induced by glutamate applied to outside-out patches were predominantly of the low-conductance class (28/19 pS).

Our data are in line with reports of NR2C subunit expression in dentate gyrus of transgenic mice. The functional expression of low-conductance NMDARs in granule cells might have important consequences for circuit function of the hippocampal formation.