ANOXIA-INDUCED LTP OF ISOLATED NMDA RECEPTOR-MEDIATED SYNAPTIC RESPONSES

1. The effects of an anoxic-aglycemic episode ( 1-3 min) on the pharma cologically isolated Ar-methyl-D-aspartate (NMDA)-mediated responses w ere examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anox ic-aglycemic episode induced a long term potentiation (LTP) of the NMD A receptor-mediated field excitatory postsynoptic potentials (EPSPs). This LTP, referred to as anoxic LTP, was observed in the presence of 1 ) a normal Mg2+ concentration [+40.1 +/- 5% (mean +/- SE) ], 2) a low Mg2+ concentration (+52.2 +/- 10%), or 3) a Mg2+ free (+49 +/- 11%), 1 h after anoxia. 3. Bath application of D-2-amino-5-phosphonovaleric a cid (D-APV, 20 muM, 15-21 min) before, during, and after the anoxicagl ycemic episode, which transiently blocked the synaptic NMDA receptor m ediated response, prevented the induction of anoxic LTP. 4. The intrac ellularly recorded NMDA receptor-mediated EPSP was also persistently p otentiated by anoxia-aglycemia (+47 +/- 4%). This potentiation was not associated with changes in membrane potential or input resistance. 5. These findings provide the first evidence that an anoxicaglycemic epi sode induces an LTP of NMDA receptor-mediated responses. This potentia tion may participate in the cascade of events that lead to delayed neu ronal death.