Zinc differentially acts on components of long-term potentiation at hippocampal CA1 synapses

Long-term potentiation (LTP) at hippocampal CA1 synapses consists of N-methyl-d-aspartate (NMDA) receptor-dependent and NMDA receptor-independent forms. The action of divalent heavy metals, which are NMDA receptor antagonists, was examined focusing on the evidence that CA1 LTP induced by a 100-Hz tetanus for 1s is abolished in the presence of 2-amino-5-phosphonovalerate (APV), a NMDA receptor antagonist. Only ZnCl2 (5microM) of heavy metals tested potentiated CA1 LTP. CA1 LTP induced by repeated 100-Hz tetanus (1s, 6 times, 10min interval), which reached a plateau in magnitude, was abolished in the presence of 50microM APV. In this case, CA1 LTP after the first tetanus was potentiated in the presence of 5microM ZnCl2, whereas CA1 LTP after the last tetanus was not potentiated. These results indicate that the magnitude of NMDA receptor-dependent CA1 LTP can be positively shifted with 5microM ZnCl2 in the range of the maximum magnitude. CA1 LTP induced by a 200-Hz tetanus for 1s was not potentiated in the presence of 5microM ZnCl2 and was partially inhibited in the presence of APV. Furthermore, CA1 LTP induced by a 200-Hz tetanus for 1s in the presence of APV was not potentiated in the presence of 5microM ZnCl2, indicating that NMDA receptor-independent CA1 LTP is not potentiated with 5microM ZnCl2. The present study suggests that zinc differentially acts on CA1 LTP components.