Whole-brain 3D mapping of human neural transplant innervation.
Whole-brain 3D mapping of human neural transplant innervation.
复制标题
人神经移植神经的全脑3D映射。
DOI：
10.1038/ncomms14162
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发表时间：
2017-01-19
影响因子：
16.6
通讯作者：
Brüstle O
中科院分区：
文献类型：
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作者：
Doerr J;Schwarz MK;Wiedermann D;Leinhaas A;Jakobs A;Schloen F;Schwarz I;Diedenhofen M;Braun NC;Koch P;Peterson DA;Kubitscheck U;Hoehn M;Brüstle O
虽然移植是评估神经干细胞体内功能及其对神经修复的适用性的关键工具，但对移植神经元整合到宿主脑回路中知之甚少。基于狂犬病病毒的逆行追踪已经发展成为一种强大的方法，用于可视化突触连接的神经元。在这里，我们结合联合收割机这种技术与光片荧光显微镜（LSFM）可视化移植细胞和连接的宿主神经元在整个小鼠脑的准备。结合高精度三维磁共振成像（3D MRI）参考数据集的配准，这种方法可以精确的解剖分配的主机输入神经元。我们的数据表明，移植到不同大脑区域的相同神经供体细胞群接受高度原位输入。这些研究结果表明，移植连接在很大程度上取决于靶区域的电路，并描绘狂犬病为基础的跨突触追踪和LSFM作为有效的工具，全面评估宿主-供体细胞神经支配。将细胞移植到中枢神经系统中已经发展成为替代因神经退行性疾病而失去的神经元的主要途径。在这里，作者开发了一种结合基于病毒的跨突触追踪标记和全脑成像的方法来追踪移植到小鼠背景中的人类神经元的突触神经支配。
While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host–donor cell innervation. Transplantation of cells into the central nervous system has developed into a major avenue for replacing neurons lost to neurodegenerative disease. Here the authors develop an approach combining viral-based transynaptic tracing labeling and whole brain imaging to trace synaptic innervation of human neurons transplanted into a mouse background.