Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution
Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution
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DOI：
10.1126/science.aau8302
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发表时间：
2019-01-18
期刊：
影响因子：
56.9
通讯作者：
Betzig, Eric
中科院分区：
文献类型：
--
作者：
Gao, Ruixuan;Asano, Shoh M.;Betzig, Eric
光学和电子显微镜在理解大脑的复杂性方面取得了巨大进展。然而，光学显微镜提供的分辨率不足以揭示亚细胞细节，而电子显微镜缺乏吞吐量和分子对比度，无法在毫米尺度或更大的尺寸上可视化特定的分子成分。我们将扩展显微镜和晶格光片显微镜结合起来，在小鼠皮层或整个果蝇大脑的厚度上对蛋白质之间的纳米级空间关系进行成像。这些包括树突棘上的突触蛋白，轴突上的髓鞘形成，以及果蝇大脑各区域多巴胺能神经元的突触前密度。这项技术应该能够在统计上丰富，大规模研究神经发育，性别二态性，刻板印象程度，以及与行为或神经活动的结构相关性，所有这些都与分子对比。
Optical and electron microscopy have made tremendous inroads toward understanding the complexity of the brain. However, optical microscopy offers insufficient resolution to reveal subcellular details, and electron microscopy lacks the throughput and molecular contrast to visualize specific molecular constituents over millimeter-scale or larger dimensions. We combined expansion microscopy and lattice light-sheet microscopy to image the nanoscale spatial relationships between proteins across the thickness of the mouse cortex or the entire Drosophila brain. These included synaptic proteins at dendritic spines, myelination along axons, and presynaptic densities at dopaminergic neurons in every fly brain region. The technology should enable statistically rich, large-scale studies of neural development, sexual dimorphism, degree of stereotypy, and structural correlations to behavior or neural activity, all with molecular contrast.