Meng Yanghong, Zhang Yu, Jia Zhengping
Program in Brain and Behavior, The Hospital for Sick Children, Toronto, Ontario, Canada.
Neuron. 2003 Jul 3;39(1):163-76. doi: 10.1016/s0896-6273(03)00368-4.
The AMPA glutamate receptor (AMPAR) subunits GluR2 and GluR3 are thought to be important for synaptic targeting/stabilization of AMPARs and the expression of hippocampal long-term depression (LTD). In order to address this hypothesis genetically, we generated and analyzed knockout mice deficient in the expression of both GluR2 and GluR3. We show here that the double knockout mice are severely impaired in basal synaptic transmission, demonstrating that GluR2/3 are essential to maintain adequate synaptic transmission in vivo. However, these mutant mice are competent in establishing several forms of long-lasting synaptic changes in the CA1 region of the hippocampus, including LTD, long-term potentiation (LTP), depotentiation, and dedepression, indicating the presence of GluR2/3-independent mechanisms of LTD expression and suggesting that AMPA receptor GluR1 alone is capable of various forms of synaptic plasticity.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体（AMPAR）亚基GluR2和GluR3被认为对AMPAR的突触靶向/稳定以及海马体长期抑制（LTD）的表达很重要。为了从基因层面验证这一假说，我们构建并分析了GluR2和GluR3表达缺失的基因敲除小鼠。我们在此表明，双基因敲除小鼠的基础突触传递严重受损，这表明GluR2/3对于在体内维持足够的突触传递至关重要。然而，这些突变小鼠在海马体CA1区建立多种形式的持久突触变化方面表现正常，包括LTD、长期增强（LTP）、去增强和再抑制，这表明存在不依赖GluR2/3的LTD表达机制，并提示单独的AMPA受体GluR1能够产生多种形式的突触可塑性。
