Mikula Shawn
Max-Planck Institute for Neurobiology, Electrons - Photons - Neurons Martinsried, Germany.
Front Neuroanat. 2016 Jun 30;10:62. doi: 10.3389/fnana.2016.00062. eCollection 2016.
Neurons are the fundamental structural units of the nervous system-i.e., the Neuron Doctrine-as the pioneering work of Santiago Ramón y Cajal in the 1880's clearly demonstrated through careful observation of Golgi-stained neuronal morphologies. However, at that time sample preparation, imaging methods and computational tools were either nonexistent or insufficiently developed to permit the precise mapping of an entire brain with all of its neurons and their connections. Some measure of the "mesoscopic" connectional organization of the mammalian brain has been obtained over the past decade by alignment of sparse subsets of labeled neurons onto a reference atlas or via MRI-based diffusion tensor imaging. Neither method, however, provides data on the complete connectivity of all neurons comprising an individual brain. Fortunately, whole-brain cellular connectomics now appears within reach due to recent advances in whole-brain sample preparation and high-throughput electron microscopy (EM), though substantial obstacles remain with respect to large volume electron microscopic acquisitions and automated neurite reconstructions. This perspective examines the current status and problems associated with generating a mammalian whole-brain cellular connectome and argues that the time is right to launch a concerted connectomic attack on a small mammalian whole-brain.
神经元是神经系统的基本结构单位，即神经元学说。19世纪80年代圣地亚哥·拉蒙·卡哈尔的开创性工作通过对高尔基染色的神经元形态进行仔细观察清楚地证明了这一点。然而，当时的样本制备、成像方法和计算工具要么不存在，要么发展不完善，无法精确绘制出包含所有神经元及其连接的整个大脑图谱。在过去十年中，通过将标记神经元的稀疏子集与参考图谱对齐或通过基于MRI的扩散张量成像，已经获得了一些关于哺乳动物大脑“介观”连接组织的测量结果。然而，这两种方法都无法提供关于构成单个大脑的所有神经元完整连接性的数据。幸运的是，由于全脑样本制备和高通量电子显微镜（EM）的最新进展，全脑细胞连接组学现在似乎触手可及，尽管在大体积电子显微镜采集和自动神经突重建方面仍然存在重大障碍。本文探讨了与生成哺乳动物全脑细胞连接组相关的现状和问题，并认为现在是对小型哺乳动物全脑发起协同连接组学研究的时机。
