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二十个人脑区域 PSD95 阳性突触的单突触分辨率调查。

A single-synapse resolution survey of PSD95-positive synapses in twenty human brain regions.

机构信息

Centre for Clinical Brain Sciences, Chancellor's Building, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.

Academic Neuropathology, Chancellor's Building, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.

出版信息

Eur J Neurosci. 2021 Oct;54(8):6864-6881. doi: 10.1111/ejn.14846. Epub 2020 Jun 25.

DOI:10.1111/ejn.14846
PMID:32492218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7615673/
Abstract

Mapping the molecular composition of individual excitatory synapses across the mouse brain reveals high synapse diversity with each brain region showing a distinct composition of synapse types. As a first step towards systematic mapping of synapse diversity across the human brain, we have labelled and imaged synapses expressing the excitatory synapse protein PSD95 in twenty human brain regions, including 13 neocortical, two subcortical, one hippocampal, one cerebellar and three brainstem regions, in four phenotypically normal individuals. We quantified the number, size and intensity of individual synaptic puncta and compared their regional distributions. We found that each region showed a distinct signature of synaptic puncta parameters. Comparison of brain regions showed that cortical and hippocampal structures are similar, and distinct from those of cerebellum and brainstem. Comparison of synapse parameters from human and mouse brain revealed conservation of parameters, hierarchical organization of brain regions and network architecture. This work illustrates the feasibility of generating a systematic single-synapse resolution atlas of the human brain, a potentially significant resource in studies of brain health and disease.

摘要

绘制小鼠大脑中单个兴奋性突触的分子组成图谱揭示了高度多样化的突触,每个脑区都显示出独特的突触类型组成。作为系统绘制人类大脑中突触多样性的第一步,我们在四个表型正常个体的 20 个人类脑区(包括 13 个皮质区、2 个皮质下区、1 个海马区、1 个小脑区和 3 个脑干区)中标记和成像表达兴奋性突触蛋白 PSD95 的突触。我们量化了单个突触小泡的数量、大小和强度,并比较了它们的区域分布。我们发现每个区域都显示出独特的突触小泡参数特征。脑区之间的比较表明,皮质和海马结构相似,与小脑和脑干不同。人类和小鼠大脑中突触参数的比较表明,参数具有保守性、脑区的层次组织和网络架构。这项工作说明了生成人类大脑系统的单突触分辨率图谱的可行性,这可能是研究大脑健康和疾病的重要资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/014d24c1b90a/EMS194245-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/8de38ab13106/EMS194245-f001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/f31513594c8c/EMS194245-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/833c9707b5ec/EMS194245-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/fcc7a54f6e73/EMS194245-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/5fb572ab5771/EMS194245-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/da834d40d7a7/EMS194245-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/014d24c1b90a/EMS194245-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/8de38ab13106/EMS194245-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/778f33713cba/EMS194245-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/f31513594c8c/EMS194245-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/833c9707b5ec/EMS194245-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/fcc7a54f6e73/EMS194245-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/5fb572ab5771/EMS194245-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/da834d40d7a7/EMS194245-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a70d/7615673/014d24c1b90a/EMS194245-f008.jpg

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