体积电子显微镜揭示了死后人类前额叶皮质中的三维突触纳米结构。
Volume electron microscopy reveals 3D synaptic nanoarchitecture in postmortem human prefrontal cortex.
作者信息
Glausier Jill R, Maier Matthew, Bouchet-Marquis Cedric, Wu Ken, Banks-Tibbs Tabitha, Melchitzky Darlene, Ning Jiying, Lewis David A, Freyberg Zachary
机构信息
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Materials and Structural Analysis, Thermo Fisher Scientific, Hillsboro, OR, USA.
出版信息
iScience. 2025 May 26;28(7):112747. doi: 10.1016/j.isci.2025.112747. eCollection 2025 Jul 18.
Synaptic function is reflected in quantifiable ultrastructural features using electron microscopy (EM) approaches. This coupling of synaptic function and ultrastructure suggests that synaptic function can be inferred from EM analysis of human brain tissue. To investigate this, we employed focused ion beam-scanning electron microscopy (FIB-SEM), a volume EM (VEM) approach, to generate ultrafine-resolution, three-dimensional (3D) micrographic datasets of postmortem human dorsolateral prefrontal cortex (DLPFC), a region with cytoarchitectonic characteristics distinct to human brain. Synaptic, sub-synaptic, and organelle measures were highly consistent with findings from experimental models that are free from antemortem or postmortem effects. Further, 3D neuropil reconstruction revealed a unique spiny dendritic shaft that exhibited several ultrastructural features characteristic of neuronal segments engaged in synaptic plasticity. Altogether, our findings provide critical proof-of-concept data demonstrating that VEM analysis appears as an effective approach to infer synaptic functioning in human brain.
使用电子显微镜（EM）方法，突触功能反映在可量化的超微结构特征中。突触功能与超微结构的这种关联表明，可以通过对人类脑组织的EM分析来推断突触功能。为了对此进行研究，我们采用了聚焦离子束扫描电子显微镜（FIB-SEM）这一体积电子显微镜（VEM）方法，来生成死后人类背外侧前额叶皮层（DLPFC）的超高分辨率三维（3D）显微图像数据集，该区域具有人类大脑独特的细胞结构特征。突触、亚突触和细胞器测量结果与不受生前或死后影响的实验模型的研究结果高度一致。此外，三维神经纤维网重建揭示了一种独特的棘状树突轴，它表现出参与突触可塑性的神经元节段的几种超微结构特征。总之，我们的研究结果提供了关键的概念验证数据，证明VEM分析似乎是推断人类大脑突触功能的有效方法。
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