NR2B-containing NMDA autoreceptors at synapses on entorhinal cortical neurons

We have previously shown that presynaptic N-methyl-D-aspartate receptors (N MDARs) can facilitate glutamate release onto principal neurons in the entor hinal cortex (EC). In the present study, we have investigated the subunit c omposition of these presynaptic NMDARs. We recorded miniature alpha -amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excit atory postsynaptic currents (mEPSCs), from visually identified neurons in l ayers II and V of the EC in vitro. In both layers, bath application of the NR2A/B subunit-selective agonist, homoquinolinic acid (HQA), resulted in a marked facilitation of mEPSC frequency. Blockade of presynaptic Ca2+ entry through either NMDARs or voltage-gated Ca2+ channels with Co2+ prevented th e effects of HQA, confirming that Ca2+ entry to the terminal was required f or facilitation. When the NR2B-selective antagonist, ifenprodil, was applie d prior to HQA, the increase in mEPSC frequency was greatly reduced. In add ition, we found that an NMDAR antagonist blocked frequency-dependent facili tation of evoked release and reduced mEPSC frequency in layer V. Thus we ha ve demonstrated that NMDA autoreceptors in layer V of the EC bear the NR2B subunit, and that NMDARs are also present at terminals onto superficial neu rons.