Preparation of mutant mice defective in the NMDA receptor channel

N-甲基-D-天冬氨酸(NMDA)受体通道在突触可塑性中起关键作用，突触可塑性被认为是学习、记忆和发育的基础。NMDA受体通道至少由谷氨酸受体(GluR)通道亚单位家族中的两个成员组成，即GluRepsilon和GluRzeta亚单位家族。这四个epsilon亚基在分布、性质和调控上各有不同。基于镁离子敏感性和表达模式，我们提出了epsilon1和epsilon2亚基在突触可塑性中的作用。在这里，我们表明，靶向干扰小鼠epsilon 1亚单位基因导致NMDA受体通道电流和海马CA1突触的长时程增强(LTP)显着减少。突变小鼠在空间学习方面也表现出中等程度的缺陷。这些结果支持这样的观点，即NMDA受体通道依赖的突触可塑性是某些形式学习的细胞基础。

The N-methyl-D-aspartate (NMDA) receptor channel plays a key role in synaptic plasticity, which is thought to underlie learning, memory and development. The NMDA receptor channel is formed by at least two members of the glutamate receptor (GluR) channel subunit families, that is, the GluRepsilon and GluRzeta subunit families. The four epsilon subunits are distinct in distribution, properties and regulation. Based on the Mg^<2+> sensitivity and expression patterns, we have proposed that the epsilon1 and epsilon2 subunits play a role in synaptic plasticity. Here we show that targeted disruption of the mouse epsilon1 subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation (LTP) at the hippocampal CA1 synapses. The mutant mice also showed moderate deficiency in spatial learning. These results support the notion that the NMDA receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.