Newton Adam J H, McDougal Robert A, Hines Michael L, Lytton William W
Department of Neuroscience, Yale University, New Haven, CT, United States.
SUNY Downstate Medical Center, The State University of New York, New York, NY, United States.
Front Neuroinform. 2018 Jul 10;12:41. doi: 10.3389/fninf.2018.00041. eCollection 2018.
Development of credible clinically-relevant brain simulations has been slowed due to a focus on electrophysiology in computational neuroscience, neglecting the multiscale whole-tissue modeling approach used for simulation in most other organ systems. We have now begun to extend the NEURON simulation platform in this direction by adding extracellular modeling. The extracellular medium of neural tissue is an active medium of neuromodulators, ions, inflammatory cells, oxygen, NO and other gases, with additional physiological, pharmacological and pathological agents. These extracellular agents influence, and are influenced by, cellular electrophysiology, and cellular chemophysiology-the complex internal cellular milieu of second-messenger signaling and cascades. NEURON's extracellular reaction-diffusion is supported by an intuitive Python-based command sequence, derived from that used for intracellular reaction diffusion, to support coarse-grained macroscopic extracellular models. This simulation specification separates the expression of the conceptual model and parameters from the underlying numerical methods. In the volume-averaging approach used, the macroscopic model of tissue is characterized by -the proportion of space in which species are able to diffuse, and the average increase in path length due to obstacles. These tissue characteristics can be defined within particular spatial regions, enabling the modeler to account for regional differences, due either to intrinsic organization, particularly gray vs. white matter, or to pathology such as edema. We illustrate simulation development using spreading depression, a pathological phenomenon thought to play roles in migraine, epilepsy and stroke. Simulation results were verified against analytic results and against the extracellular portion of the simulation run under FiPy. The creation of this NEURON interface provides a pathway for interoperability that can be used to automatically export this class of models into complex intracellular/extracellular simulations and future cross-simulator standardization.
由于计算神经科学专注于电生理学，忽视了大多数其他器官系统模拟中使用的多尺度全组织建模方法，可信的临床相关脑模拟的发展一直受到阻碍。我们现在已开始通过添加细胞外建模，朝着这个方向扩展NEURON模拟平台。神经组织的细胞外介质是神经调节剂、离子、炎症细胞、氧气、一氧化氮和其他气体的活性介质，还有其他生理、药理和病理因子。这些细胞外因子影响细胞电生理学以及细胞化学生理学（第二信使信号传导和级联反应的复杂细胞内环境），同时也受到它们的影响。NEURON的细胞外反应扩散由基于直观的Python命令序列支持，该序列源自用于细胞内反应扩散的序列，以支持粗粒度的宏观细胞外模型。这种模拟规范将概念模型和参数的表达与底层数值方法分开。在使用的体积平均方法中，组织的宏观模型由物种能够扩散的空间比例以及由于障碍物导致的路径长度平均增加来表征。这些组织特征可以在特定空间区域内定义，使建模者能够考虑由于内在组织（特别是灰质与白质）或病理（如水肿）引起的区域差异。我们使用扩散性抑制来说明模拟开发，扩散性抑制是一种被认为在偏头痛、癫痫和中风中起作用的病理现象。模拟结果与解析结果以及在FiPy下运行的模拟的细胞外部分进行了验证。这个NEURON接口的创建提供了一条互操作性途径，可用于自动将这类模型导出到复杂的细胞内/细胞外模拟以及未来的跨模拟器标准化中。
