PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits.
PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits.
复制标题
DOI：
10.1038/srep24626
复制
发表时间：
2016-04-25
影响因子：
4.6
通讯作者：
Grant SG
中科院分区：
文献类型：
--
作者：
Broadhead MJ;Horrocks MH;Zhu F;Muresan L;Benavides-Piccione R;DeFelipe J;Fricker D;Kopanitsa MV;Duncan RR;Klenerman D;Komiyama NH;Lee SF;Grant SG
海马体中突触的分子特征是当前学习和认知模型的基础。虽然突触超微结构的多样性已被描述在典型的海马电路，我们的知识突触分子的突触下组织仍然在很大程度上是未知的。为了解决这一问题，将小鼠工程化以表达与eGFP或mEos 2融合的突触后密度95蛋白（PSD 95），并使用两种正交超分辨率方法进行成像：门控受激发射耗尽（g-STED）显微镜和光活化定位显微镜（PALM）。对7个海马子区域中约100，000个突触的大规模分析显示，它们包含离散的PSD 95纳米簇，这些纳米簇在空间上组织成单个和多个纳米簇PSD。突触在不同的子区域，细胞类型和位置沿着的树突树的CA 1锥体神经元，表现出多样性的特点是每个突触的纳米簇的数量。多纳米簇突触常见于CA 3和齿状回亚区，对应于大的多刺赘生物突触。虽然各个纳米团簇的结构在所有子区域中保持相对保守，但填充到纳米团簇中的PSD 95也在由纳米团簇荧光强度确定的子区域之间变化。这些数据将PSD 95纳米簇鉴定为兴奋性突触的基本结构单元或构建块，并且它们的数量表征突触大小和结构多样性。
The molecular features of synapses in the hippocampus underpin current models of learning and cognition. Although synapse ultra-structural diversity has been described in the canonical hippocampal circuitry, our knowledge of sub-synaptic organisation of synaptic molecules remains largely unknown. To address this, mice were engineered to express Post Synaptic Density 95 protein (PSD95) fused to either eGFP or mEos2 and imaged with two orthogonal super-resolution methods: gated stimulated emission depletion (g-STED) microscopy and photoactivated localisation microscopy (PALM). Large-scale analysis of ~100,000 synapses in 7 hippocampal sub-regions revealed they comprised discrete PSD95 nanoclusters that were spatially organised into single and multi-nanocluster PSDs. Synapses in different sub-regions, cell-types and locations along the dendritic tree of CA1 pyramidal neurons, showed diversity characterised by the number of nanoclusters per synapse. Multi-nanocluster synapses were frequently found in the CA3 and dentate gyrus sub-regions, corresponding to large thorny excrescence synapses. Although the structure of individual nanoclusters remained relatively conserved across all sub-regions, PSD95 packing into nanoclusters also varied between sub-regions determined from nanocluster fluorescence intensity. These data identify PSD95 nanoclusters as a basic structural unit, or building block, of excitatory synapses and their number characterizes synapse size and structural diversity.