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.