A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset
A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset
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DOI：
10.7554/elife.40042
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发表时间：
2019-02-05
期刊：
影响因子：
7.7
通讯作者：
Mitra, Partha
中科院分区：
文献类型：
--
作者：
Lin, Meng Kuan;Takahashi, Yeonsook Shin;Mitra, Partha
了解整个脊椎动物大脑的连接结构是一项基本但困难的任务。在这里，我们提出了一个完整的神经组织学管道以及一个基于网格的示踪剂注射策略，用于系统地绘制普通绒猴(Callithrix Jacchus)的中尺度连接图。使用胶带传输技术将单个大脑切片成类似1700个20米长的切片，从而实现一系列组织化学染色(尼氏、髓鞘)与示踪剂标记切片交错的高质量3D重建。个体动物的系统体内核磁共振成像有助于将注射放置到参考图谱定义的解剖间隔中。此外，通过将生成的包含信息的细胞结构标记的3D体积与体内和体外MRI相结合，并使用集成的计算管道，我们能够准确地将个体大脑映射到共同的参考图谱中，尽管个体差异很大。这种方法将促进中尺度连接矩阵的系统组装，以及史无前例的灵长类大脑全脑投影模式的3D重建。
Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. Here we present an integrated neuro-histological pipeline as well as a grid-based tracer injection strategy for systematic mesoscale connectivity mapping in the common marmoset (Callithrix jacchus). Individual brains are sectioned into similar to 1700 20 m m sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labeled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments. Further, by combining the resulting 3D volumes, containing informative cytoarchitectonic markers, with in-vivo and ex-vivo MRI, and using an integrated computational pipeline, we are able to accurately map individual brains into a common reference atlas despite the significant individual variation. This approach will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain.