An Accessible Optical Toolbox for Saturated Nanoscale Analysis of Neural Architecture

神经元完整结构的纳米级分辨率重建提供了 有可能彻底改变正常和患病大脑中神经元回路的研究 但这一承诺远未实现，因为更大的神经科学界无法 访问提供大量纳米级重建的技术， 分析它们所需的计算基础设施。因此，神经解剖学在 纳米尺度仅限于对较小体积的一次性研究， 在单个动物中进行小体积重建（n<=1），并且仅可由 能够负担得起所需的非凡的时间承诺，劳动力和费用， 重建简单的神经回路在这里，我们提出了一种新的方法： 而不是开发越来越复杂的硬件， 大脑，我们建议开发一个可访问的分子，化学， 计算方法的准确纳米级重建的大量的 大脑靶向荧光显微镜和传统的共聚焦显微镜- 神经科学武器库中最广泛使用的两种工具。通过提供 重建脑细胞之间的自然形状和空间 在大范围的实验条件下，在活体大脑中发现，我们将帮助提供 从全面的纳米神经解剖学到更广泛的神经科学 社区

Nanoscale-resolution reconstructions of the complete architectures of neurons offer the potential to revolutionize the study of neuronal circuitry in normal and diseased brains but this promise is far from realized because the larger neuroscience community cannot access the technologies that provide nanoscale reconstructions over large volumes and the computational infrastructure required to analyze them. As a result, neuroanatomy at the nanoscale is restricted to one-off studies of smaller volumes, rarely extending past small volume reconstructions in single animals (n<=1), and accessible only to labs that can afford the extraordinary time commitment, labor, and expense required to reconstruct even simple neuronal circuits. Here we propose a novel approach: rather than developing more and more sophisticated hardware for nanoscale reconstructions of the brain, we propose to develop a toolbox of accessible molecular, chemical, and computational approaches for accurate nanoscale reconstructions of large volumes of the brain targeting fluorescence microscopy and the conventional confocal microscope – two of the most widely accessed tools in the neuroscience arsenal. By providing an accessible pipeline to reconstructing the natural shape and space between brain cells found in the living brain over wide range of experimental conditions, we will help deliver access to comprehensive nanoscale neuroanatomy to the broader neuroscience community.