Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics.
Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics.
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DOI：
10.1523/jneurosci.4630-08.2009
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发表时间：
2009-05-13
期刊：
影响因子：
--
通讯作者：
Zhu JJ
中科院分区：
文献类型：
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作者：
Zhu JJ
中枢谷氨酸能突触可以表达具有不同门控特性的AMPA敏感性谷氨酸受体（AMPA-R），并表现出不同的传输动力学，这对于计算在不同突触群体处接收的各种突触输入是重要的。然而，AMPA-R是如何通过不同的动力学机制影响突触整合的，目前还不清楚。在这里，我报告突触特定的贩运不同的AMPA-R在大鼠皮质层4星状和层5锥体神经元。分析表明，在单层4星状神经元中，丘脑皮质突触比皮质内突触产生更快的突触反应。此外，含有GluR 1的AMPA-R选择性地进入皮质内突触，这一过程需要感觉经验依赖性活动，并减缓传输动力学。含有GluR 4的AMPA-R比皮质内突触更频繁地进入丘脑皮质突触，这一过程需要自发的突触活动并加快传递动力学。含有GluR 2的AMPA-R同样进入丘脑皮质和皮质内突触，这个过程不需要突触活动，并重置传输动力学。值得注意的是，不同AMPA-R的突触运输差异调节突触整合。因此，突触特异性AMPA-R运输粗集和突触活动精细地调谐在中枢神经元中的不同突触处的传递动力学和整合特性。
Central glutamatergic synapses may express AMPA-sensitive glutamate receptors (AMPA-Rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. However, how glutamatergic synapses acquire AMPA-Rs with distinct kinetics to influence synaptic integration remains poorly understood. Here I report synapse-specific trafficking of distinct AMPA-Rs in rat cortical layer 4 stellate and layer 5 pyramidal neurons. The analysis indicates that in single layer 4 stellate neurons thalamocortical synapses generate faster synaptic responses than intracortical synapses. Moreover, GluR1-containing AMPA-Rs traffic selectively into intracortical synapses, and this process requires sensory experience-dependent activity and slows down transmission kinetics. GluR4-containing AMPA-Rs traffic more heavily into thalamocortical synapses than intracortical synapses, and this process requires spontaneous synaptic activity and speeds up transmission kinetics. GluR2-containing AMPA-Rs traffic equally into both thalamocortical and intracortical synapses, and this process requires no synaptic activity and resets transmission kinetics. Notably, synaptic trafficking of distinct AMPA-Rs differentially regulates synaptic integration. Thus, synapse-specific AMPA-R trafficking coarsely sets and synaptic activity finely tunes transmission kinetics and integration properties at different synapses in central neurons.