Synaptic AMPA receptor exchange maintains bidirectional plasticity
Synaptic AMPA receptor exchange maintains bidirectional plasticity
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DOI：
10.1016/j.neuron.2006.02.027
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发表时间：
2006-04-06
期刊：
影响因子：
16.2
通讯作者：
Zhu, JJ
中科院分区：
文献类型：
--
作者：
McCormack, SG;Stornetta, RL;Zhu, JJ
含 GluR1、GluR2L 和 GluR4 的 AMPA 受体 (-R) 的活性依赖性突触传递和含 GluR2 的 AMPA-R 的去除分别介导突触增强和抑制。明显的难题是，如果使用不同的 AMPA-R 来增强和抑制，突触如何保持双向可塑性的能力。在这里，我们表明突触 AMPA-R 交换对于维持双向可塑性能力至关重要。该交换过程包括在体外和完整大脑中，在海马和皮质突触中以与活动无关的方式去除含有 GluR1、GluR2L 或 GluR4 的 AMPA-R，并用含有 GluR2 的 AMPA-R 重新填充。在 GluR1 和 GiuR2 敲除小鼠中，突触 AMPA-R 交换的启动或完成分别受到损害。交换过程中互补的 AMPA-R 去除和重新填充事件最终保持突触强度不变，但它们的长速率时间常数（类似于 15-18 小时）导致传输在交换过程中暂时抑制。这些结果表明，之前假设的“槽”蛋白，而不是 AMPA-R，编码并维持中央突触的传输效率。
Activity-dependent synaptic delivery of GluR1-, GluR2L-, and GluR4-containing AMPA receptors (-Rs) and removal of GluR2-containing AMPA-Rs mediate synaptic potentiation and depression, respectively. The obvious puzzle is how synapses maintain the capacity for bidirectional plasticity if different AMPA-Rs are utilized for potentiation and depression. Here, we show that synaptic AMPA-R exchange is essential for maintaining the capacity for bidirectional plasticity. The exchange process consists of activity-independent synaptic removal of GluR1-, GluR2L-, or GluR4-containing AMPA-Rs and refilling with GluR2-containing AMPA-Rs at hippocampal and cortical synapses in vitro and in intact brains. In GluR1 and GiuR2 knockout mice, initiation or completion of synaptic AMPA-R exchange is compromised, respectively. The complementary AMPA-R removal and refilling events in the exchange process ultimately maintain synaptic strength unchanged, but their long rate time constants (similar to 15-18 hr) render transmission temporarily depressed in the middle of the exchange. These results suggest that the previously hypothesized "slot" proteins, rather than AMPA-Rs, code and maintain transmission efficacy at central synapses.