The hippocampus is important in learning and memory and is particularly susceptible to delayed cell death following stroke. Within the hippocampus, there is evidence that CA1 pyramidal neurones are more susceptible to ischaemic damage than cells in the CA3 region, but exact reasons why remain unknown. One major excitatory postsynaptic receptors within the hippocampus is the AMPA receptor (AMPAR). The plasticity of AMPA receptors in postsynaptic hippocampal slices following oxygen glucose deprivation (OGD), conditions believed to replicate those found in ischaemia, has previously been demonstrated in CA1 pyramidal neurones where synaptic AMPAR subunit switching occurs following OGD [1]. Here we show a selective substantial decrease in AMPAR excitatory postsynaptic currents (EPSCs) following OGD at associational-commissural (AC) synapses in the CA3 area but not at CA1 Schaffer collateral synapses.<p> Experiments were performed using hippocampal slices taken from postnatal day (P) 13-15 rats. Whole-cell patch clamp recordings and extracellular field potential recordings were made in the presence of the NMDAR antagonist Ly-689,560 (5µM) and GABAA receptor antagonist picrotoxin (100µM) to investigate changes in AMPAR trafficking at the membrane in response to 15 minutes OGD (O2 and glucose replaced with N2 and sucrose respectively).<P> OGD resulted in a substantial and long-lasting loss of AMPAR-mediated EPSCs on CA3 pyramidal neurones (86±14%, n=7). The fibre volley amplitude was transiently depressed during OGD, followed by a full recovery within 30 minutes (107±18%, n=7) suggesting that the decrease in AMPAR EPSC amplitude was not due to a loss of presynaptic firing. Further evidence for a postsynaptic AMPAR loss was demonstrated by measuring responses to exogenous glutamate (10mM) application to evoke AMPAR-mediated responses. Responses to exogenous glutamate were also depressed following OGD (4±2% n=9). The effect was specific to AMPARs and localised within the CA3 region as NMDAR-mediated EPSCs and Schaffer collateral synaptic responses in CA1 both recovered following OGD (63±10% n=11 and 77±24%, n=4). The addition of 2mM Kynurenate during OGD failed to recover the AMPAR EPSC (1±2%, n=8), suggesting that the loss of the AMPAR EPSC is not dependent on AMPAR activation. However, removal of Ca2+ from the external solution during OGD (71±7%, n=10), or the addition of 50μM BAPTA to the intracellular solution (78±10%, n=10), was able to prevent the loss of AMPAR EPSCs normally observed. <P> We conclude that there is a selective decrease of postsynaptic AMPAR EPSC at AC synapses within the CA3 region of the hippocampus following OGD that is not mediated by NMDAR or AMPAR activation but requires a rise in intracellular Ca2+.