Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells
Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells
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DOI：
10.1152/jn.1999.82.2.526
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发表时间：
1999-08-01
影响因子：
2.5
通讯作者：
Lisman, J
中科院分区：
文献类型：
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作者：
Chen, HX;Otmakhov, N;Lisman, J
在海马CA1区诱导长时程增强(LTP)既需要突触前活动，也需要大量突触后去极化。使用全细胞记录诱导LTP的标准方案是将低频突触刺激(100-200个脉冲，1-2赫兹)与去极化电压钳脉冲(1-3分钟持续时间)配对。在该标准协议中，使用了基于Cs+的内部解决方案来提高电压钳制产生的去极化的保真度。为了更快地诱导LTP，我们尝试了高频刺激(200个脉冲，20-100赫兹)和短去极化(类似于15 S)的组合来诱导LTP。令人惊讶的是，我们发现该方案未能诱导LTP，即使在同一细胞中后续的标准方案可以诱导较大的LTP(类似于基线的300%)。在长时间去极化(3min)开始时，配对短暂的高频刺激也不能诱导LTP。然而，在长去极化结束时，同样的高频刺激确实诱导了LTP。当以K+为基础的内部溶液进行类似的实验时，高频刺激和短去极化搭配确实会诱导LTP。这表明，对长退极化的要求与Cs+的使用有关。我们推测，当用Cs+进行记录时，在去极化开始时给予的破伤风启动了一个抑制N-甲基-D-天冬氨酸(NMDA)依赖的LTP的过程。在长时间的去极化过程中，这种抑制过程本身就会消失。
The induction of long-term potentiation (LTP) in the hippocampal CA1 region requires both presynaptic activity and large postsynaptic depolarization. A standard protocol for inducing LTP using whole-cell recording is to pair low-frequency synaptic stimulation (100-200 pulses, 1-2 Hz) with a depolarizing voltage-clamp pulse (1-3 min duration). In this standard protocol, a Cs+-based internal solution is used to improve the fidelity of the depolarization produced by voltage-clamp. In an attempt to induce LTP more rapidly, we tried to induce LTP by pairing high-frequency stimulation (200 pulses, 20-100 Hz) with a short depolarization (similar to 15 s). Surprisingly, we found that this protocol failed to induce LTP, even though large LTP (similar to 300% of baseline) could be induced by a subsequent standard protocol in the same cell. Pairing brief high-frequency stimulation at the beginning of a long depolarization (3 min) also did not induce LTP. However, the same high-frequency stimulation at the end of the long depolarization did induce LTP. When similar experiments were done with a K+-based internal solution, pairing high-frequency stimulation with a short depolarization did induce LTP. This indicates that the requirement for long depolarization is related to the use of Cs+. We speculate that, when recording is made with Cs+, a tetanus given at the beginning of depolarization initiates a process that inhibits N-methyl-D-aspartate (NMDA)-dependent LTP. This inhibitory process itself decays away during prolonged depolarization.