There is good evidence that changing the number of synaptic AMPARs is an important mechanism underlying synaptic plasticity. We have shown that whole-cell perfusion of the IP3R agonist adenophostin strongly potentiates AMPA receptor-mediated EPSCs via intracellular Ca2+ release (Maher and Kelly, SFN Abstr. # 923.2, 2001), and this potentiation is mediated through a SNARE-dependent mechanism (Maher, et.al., SFN Abstr. # 150.1, 2002). Recently, the trafficking of synaptic NMDARs has been shown to be associated with synaptic plasticity (Carroll and Zukin, TINS 2002, 25(11):571-7). We are exploring the possibility that intracellular Ca2+ release can modulate postsynaptic NMDA EPSCs. We observed that whole-cell perfusion of adenophostin can significantly increase pharmacologically isolated NMDA EPSCs monitored in ACSF containing 0.8 mM Mg2+, 10 µM CNQX, and 50 µM PTX at -30 mV holding potential. In addition, co-perfusion of 5 mM BAPTA can block the intracellular Ca2+-induced increase in NMDA EPSCs observed with...