Anoxia-induced LTP of isolated NMDA receptor-mediated synaptic responses.
1. The effects of an anoxic-aglycemic episode (1-3 min) on the pharmacologically isolated N-methyl-D-aspartate (NMDA)-mediated responses were examined in CA1 pyramidal hippocampal neurons in vitro. 2. An anoxic-aglycemic episode induced a long term potentiation (LTP) of the NMDA receptor-mediated field excitatory post-synoptic 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 acid (D-APV, 20 microM, 15-21 min) before, during, and after the anoxic-aglycemic episode, which transiently blocked the synaptic NMDA receptor mediated response, prevented the induction of anoxic LTP. 4. The intracellularly recorded NMDA receptor-mediated EPSP was also persistently potentiated 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 anoxic-aglycemic episode induces an LTP of NMDA receptor-mediated responses. This potentiation may participate in the cascade of events that lead to delayed neuronal death.
Crepel
V
V
Institut National de la Santé et de la Recherche Médicale U-29, Paris, France.
Hammond
C
C
Krnjevic
K
K
Chinestra
P
P
Ben-Ari
Y
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D046508:Culture Techniques; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate