Memory and long-term potentiation (LTP) dissociated:: Normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense
Memory and long-term potentiation (LTP) dissociated:: Normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense
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DOI：
10.1073/pnas.95.25.15037
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Alkon, DL
中科院分区：
文献类型：
--
作者：
Meiri, N;Sun, MK;Alkon, DL
海马切片制备中的长时程增强（LTP）已被提议作为长期记忆的体外模型。然而，LTP 与活体动物记忆的相关性一直难以证明。此外，在过去几年中，越来越多的证据表明这两者是分离的。由于钾通道可能决定网络中突触的权重，因此我们研究了 Kv1.4（一种突触前 A 型电压依赖性 K+ 通道）在记忆和 LTP 中的作用。逆转录-PCR 和特异性抗体的蛋白质印迹分析表明，将 Kv1.4 反义寡脱氧核糖核苷酸微量注射到大鼠大脑中会阻碍海马 Kv1.4 mRNA，“敲低”海马中的蛋白质。这种反义敲除对大鼠空间迷宫学习、记忆或探索行为没有影响，但消除了早期和晚期 LTP，并减少了 CA1 锥体神经元中的配对脉冲促进（突触前效应），而不影响齿状回 LTP。这种突触前 Kv1.4 敲低与之前的突触后 Kv1.1 敲低一起表明 CA1 LTP 对于大鼠空间记忆既不是必要的也不是充分的。
Long-term potentiation (LTP) in the hippocampal slice preparation has been proposed as an in vitro model for long-term memory. However, correlation of LTP with memory in living animals has been difficult to demonstrate. Furthermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in networks, we studied the role of Kv1.4, a presynaptic A-type voltage-dependent K+ channel, in both memory and LTP. Reverse transcription-PCR and Western blot analysis with specific antibodies showed that antisense oligodeoxyribonucleotide to Kv1.4 microinjected intraventricularly into rat brains obstructed hippocampal Kv1.4 mRNA, "knocking down" the protein in the hippocampus. This antisense knockdown had no effect on rat spatial maze learning, memory, or exploratory behavior, but eliminated both early- and late-phase LTP and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyramidal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 knockdown together with previous postsynaptic Kv1.1 knockdown demonstrates that CA1 LTP is neither necessary nor sufficient for rat spatial memory.