Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Neuron. 2013 May 22;78(4):615-22. doi: 10.1016/j.neuron.2013.03.009.
Scaffolding molecules at the postsynaptic membrane form the foundation of excitatory synaptic transmission by establishing the architecture of the postsynaptic density (PSD), but the small size of the synapse has precluded measurement of PSD organization in live cells. We measured the internal structure of the PSD in live neurons at approximately 25 nm resolution using photoactivated localization microscopy (PALM). We found that four major PSD scaffold proteins were each organized in distinctive ∼80 nm ensembles able to undergo striking changes over time. Bidirectional PALM and single-molecule immunolabeling showed that dense nanodomains of PSD-95 were preferentially enriched in AMPA receptors more than NMDA receptors. Chronic suppression of activity triggered changes in PSD interior architecture that may help amplify synaptic plasticity. The observed clustered architecture of the PSD controlled the amplitude and variance of simulated postsynaptic currents, suggesting several ways in which PSD interior organization may regulate the strength and plasticity of neurotransmission.
突触后膜上的支架分子通过建立突触后密度（PSD）的结构，为兴奋性突触传递奠定了基础，但由于突触的体积较小，一直无法在活细胞中测量 PSD 的组织情况。我们使用光激活定位显微镜（PALM）以大约 25nm 的分辨率测量了活神经元中 PSD 的内部结构。我们发现，四种主要的 PSD 支架蛋白各自以独特的约 80nm 聚集体的形式组织，能够随时间发生显著变化。双向 PALM 和单分子免疫标记显示，PSD-95 的致密纳米域优先富集 AMPA 受体而不是 NMDA 受体。活性的慢性抑制会引发 PSD 内部结构的变化，这可能有助于放大突触可塑性。观察到的 PSD 聚类结构控制了模拟突触后电流的幅度和方差，这表明 PSD 内部组织可能通过几种方式调节神经递质传递的强度和可塑性。
