Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute Houston, TX, USA ; TT and WF Chao Center for Bioinformatics Research and Imaging for Neurosciences, Houston Methodist Research Institute Houston, TX, USA.
Front Neuroanat. 2014 Nov 12;8:130. doi: 10.3389/fnana.2014.00130. eCollection 2014.
Comprising 10(11) neurons with 10(14) synaptic connections the human brain is the ultimate systems biology puzzle. An increasing body of evidence highlights the observation that changes in brain function, both normal and pathological, consistently correlate with dynamic changes in neuronal anatomy. Anatomical changes occur on a full range of scales from the trafficking of individual proteins, to alterations in synaptic morphology both individually and on a systems level, to reductions in long distance connectivity and brain volume. The major sites of contact for synapsing neurons are dendritic spines, which provide an excellent metric for the number and strength of signaling connections between elements of functional neuronal circuits. A comprehensive model of anatomical changes and their functional consequences would be a holy grail for the field of systems neuroscience but its realization appears far on the horizon. Various imaging technologies have advanced to allow for multi-scale visualization of brain plasticity and pathology, but computational analysis of the big data sets involved forms the bottleneck toward the creation of multiscale models of brain structure and function. While a full accounting of techniques and progress toward a comprehensive model of brain anatomy and function is beyond the scope of this or any other single paper, this review serves to highlight the opportunities for analysis of neuronal spine anatomy and function provided by new imaging technologies and the high-throughput application of older technologies while surveying the strengths and weaknesses of currently available computational analytical tools and room for future improvement.
人类大脑由 10(11)个神经元组成，有 10(14)个突触连接，是终极的系统生物学难题。越来越多的证据表明，大脑功能的变化，无论是正常的还是病理性的，都与神经元解剖结构的动态变化一致。解剖结构的变化发生在从单个蛋白质的运输到单个和系统水平上的突触形态变化，再到远距离连接和脑体积减少的各种规模上。神经元突触的主要接触点是树突棘，它为功能神经元回路中元素之间的信号连接的数量和强度提供了一个极好的衡量标准。一个全面的解剖结构变化及其功能后果模型将是系统神经科学领域的圣杯，但它的实现似乎还很遥远。各种成像技术已经发展到可以对大脑可塑性和病理学进行多尺度可视化，但涉及的大数据集的计算分析是创建大脑结构和功能多尺度模型的瓶颈。虽然全面描述技术以及构建大脑解剖和功能综合模型的进展超出了本文或任何其他单一论文的范围，但本文旨在强调新成像技术为分析神经元棘突解剖和功能提供的机会，以及旧技术的高通量应用，同时调查当前可用计算分析工具的优缺点以及未来改进的空间。
