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 1 s is abolished in the presence of 2-amino-5-phosphonovalerate (APV), a NMDA receptor antagonist. Only ZnCl2 (5 μM) of heavy metals tested potentiated CA1 LTP. CA1 LTP induced by repeated 100-Hz tetanus (1 s, 6 times, 10 min interval), which reached a plateau in magnitude, was abolished in the presence of 50 μM APV. In this case, CA1 LTP after the first tetanus was potentiated in the presence of 5 μM 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 5 μM ZnCl2 in the range of the maximum magnitude. CA1 LTP induced by a 200-Hz tetanus for 1 s was not potentiated in the presence of 5 μM ZnCl2 and was partially inhibited in the presence of APV. Furthermore, CA1 LTP induced by a 200-Hz tetanus for 1 s in the presence of APV was not potentiated in the presence of 5 μM ZnCl2, indicating that NMDA receptor-independent CA1 LTP is not potentiated with 5 μM ZnCl2. The present study suggests that zinc differentially acts on CA1 LTP components.