海馬CA1ニューロンのシナプス可塑性におけるプレコンディショニング刺激効果は代謝型グルタミン酸受容体の活性化に依存する

抄録

In hippocampal CA1 neurons, delivery of low-frequency afferent stimuli <LFS;80 pulses at 1 Hz> induced LTP in both the field EPSP and population spike <PS>. In the same cells, reversal of LTP in the EPSP and PS was achieved by the same LFS given 20 min after the first LFS <second LFS>. We investigated the effects of metabotropic glutamate receptor <mGluR> antagonists on LTP or LTD induced by the second LFS. When the first LFS was given in the standard solution, both the field EPSP and PS were attenuated by the second LFS. In contrast, when the first LFS was delivered in the presence of MCPG, a broad spectrum mGluR antagonist or 4CPG, a type 1 mGluR antagonist, the field EPSP and PS were enhanced by the second LFS. Thus, activation of mGluRs during preconditioning LFS stimulation determines the direction of synaptic plasticity at CA1 neurons. Then, we investigated the effects of an NMDA receptor antagonist, AP5 on synaptic plasticity induced by the second LFS. When the first LFS was given in the standard solution or in 4CPG but the second LFS was given in the presence of AP5, both the EPSP and PS were enhanced after the second LFS. These results indicate that the synaptic plasticity induced by the second LFS depends on NMDA receptor activation at CA1 synapses. Thus, it is possible that activation of mGluRs during prior synaptic activation resulted in enhancement of NMDA receptor activation, leading to reversal of LTP. [J Physiol Sci. 2006;56 Suppl:S87]