Distribution, density, and clustering of functional glutamate receptors before and after synaptogenesis in hippocampal neurons
Distribution, density, and clustering of functional glutamate receptors before and after synaptogenesis in hippocampal neurons
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DOI：
10.1152/jn.2000.84.3.1573
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发表时间：
2000-09-01
影响因子：
2.5
通讯作者：
Liu, GS
中科院分区：
文献类型：
--
作者：
Cottrell, JR;Dubé, GR;Liu, GS
突触后分化过程中的突触能突触的形成知之甚少。使用一种新的生物物理方法，我们已经调查了功能性谷氨酸受体的分布和密度，并在培养的海马神经元突触发生过程中，其集群的特点。我们发现功能性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）和N-甲基-D-天冬氨酸（NMDA）受体在突触发生前均匀分布在树突细胞膜上，估计密度为3个受体/μ m（2）。在突触发生后，功能性AMPA和NMDA受体聚集在突触处，其密度估计为10（4）个受体/μ m（2）的数量级，这对应于类似于400个受体/突触。同时，突触外受体密度没有减少，这表明现有受体池的聚集不是谷氨酸受体聚集的主要机制。此外，我们的数据表明，AMPA与NMDA受体密度的比例可能被调节为在所有树突位置接近1。我们还表明，突触AMPA和NMDA受体簇的形式与一个类似的时间过程中的突触和功能AMPA受体集群独立的活动和谷氨酸受体激活，包括以下删除的NMDA受体NR 1亚基。因此，谷氨酸受体激活不是突触形成过程中功能性AMPA受体的插入、聚集和激活所必需的，并且该过程可能由活性独立信号控制。
Postsynaptic differentiation during glutamatergic synapse formation is poorly understood. Using a novel biophysical approach, we have investigated the distribution and density of functional glutamate receptors and characterized their clustering during synaptogenesis in cultured hippocampal neurons. We found that functional alpha- amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors are evenly distributed in the dendritic membrane before synaptogenesis with an estimated density of 3 receptors/mu m(2). Following synaptogenesis, functional AMPA and NMDA receptors are clustered at synapses with a density estimated to be on the order of 10(4) receptors/mu m(2), which corresponds to similar to 400 receptors/synapse. Meanwhile there is no reduction in the extrasynaptic receptor density, which indicates that the aggregation of the existing pool of receptors is not the primary mechanism of glutamate receptor clustering. Furthermore our data suggest that the ratio of AMPA to NMDA receptor density may be regulated to be close to one in all dendritic locations. We also demonstrate that synaptic AMPA and NMDA receptor clusters form with a similar time course during synaptogenesis and that functional AMPA receptors cluster independently of activity and glutamate receptor activation, including following the deletion of the NMDA receptor NR1 subunit. Thus glutamate receptor activation is not necessary for the insertion, clustering, and activation of functional AMPA receptors during synapse formation, and this process is likely controlled by an activity-independent signal.