Input-Specific Intrasynaptic Arrangements of Ionotropic Glutamate Receptors and Their Impact on Postsynaptic Responses
Input-Specific Intrasynaptic Arrangements of Ionotropic Glutamate Receptors and Their Impact on Postsynaptic Responses
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DOI：
10.1523/jneurosci.6160-08.2009
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发表时间：
2009-10-14
影响因子：
5.3
通讯作者：
Shigemoto, Ryuichi
中科院分区：
文献类型：
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作者：
Tarusawa, Etsuko;Matsui, Ko;Shigemoto, Ryuichi
为了研究突触后受体的突触内排列与突触的功能作用的关系，我们定量分析了AMPA和NMDA受体（AMPARs和NMDARs，分别）的二维分布，使用SDS消化的冷冻断裂复制标记（SDS-FRL）和评估分布差异对突触后反应的影响通过模拟。在背外侧膝状体，皮质膝状体（CG）突触的两倍大，视网膜膝状体（RG）突触，但表达类似数量的AMPAR。复制品的二维视图显示，AMPAR在两个突触中以相似的程度形成微簇，导致CG突触中更大的AMPAR缺乏区域。尽管在突触内的AMPAR分布的广泛差异，我们的模拟的基础上，实际的受体分布表明，在个别RG突触的AMPAR量子响应仅略大于振幅，较少的变量，并在动力学上比CG突触具有类似数量的受体更快。CG突触的NMDAR表达是RG突触的两倍。电生理记录证实了更大的贡献NMDAR相对于AMPAR介导的反应在CG突触。我们的结论是突触的大小和受体的密度和分布有轻微的影响量子响应和受体的数量作为一个主要的突触后决定因素介导的AMPAR和NMDAR的突触强度。
To examine the intrasynaptic arrangement of postsynaptic receptors in relation to the functional role of the synapse, we quantitatively analyzed the two-dimensional distribution of AMPA and NMDA receptors (AMPARs and NMDARs, respectively) using SDS-digested freeze-fracture replica labeling (SDS-FRL) and assessed the implication of distribution differences on the postsynaptic responses by simulation. In the dorsal lateral geniculate nucleus, corticogeniculate (CG) synapses were twice as large as retinogeniculate (RG) synapses but expressed similar numbers of AMPARs. Two-dimensional views of replicas revealed that AMPARs form microclusters in both synapses to a similar extent, resulting in larger AMPAR-lacking areas in the CG synapses. Despite the broad difference in the AMPAR distribution within a synapse, our simulations based on the actual receptor distributions suggested that the AMPAR quantal response at individual RG synapses is only slightly larger in amplitude, less variable, and faster in kinetics than that at CG synapses having a similar number of the receptors. NMDARs at the CG synapses were expressed twice as many as those in the RG synapses. Electrophysiological recordings confirmed a larger contribution of NMDAR relative to AMPAR-mediated responses in CG synapses. We conclude that synapse size and the density and distribution of receptors have minor influences on quantal responses and that the number of receptors acts as a predominant postsynaptic determinant of the synaptic strength mediated by both the AMPARs and NMDARs.