McDougal Robert A, Conte Cameron, Eggleston Lia, Newton Adam J H, Galijasevic Hana
Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States.
Center for Medical Informatics, Yale University, New Haven, CT, United States.
Front Neuroinform. 2022 May 17;16:847108. doi: 10.3389/fninf.2022.847108. eCollection 2022.
Neuronal activity is the result of both the electrophysiology and chemophysiology. A neuron can be well-represented for the purposes of electrophysiological simulation as a tree composed of connected cylinders. This representation is also apt for 1D simulations of their chemophysiology, provided the spatial scale is larger than the diameter of the cylinders and there is radial symmetry. Higher dimensional simulation is necessary to accurately capture the dynamics when these criteria are not met, such as with wave curvature, spines, or diffusion near the soma. We have developed a solution to enable efficient finite volume method simulation of reaction-diffusion kinetics in intracellular 3D regions in neuron and network models and provide an implementation within the NEURON simulator. An accelerated version of the CTNG 3D reconstruction algorithm transforms morphologies suitable for ion-channel based simulations into consistent 3D voxelized regions. Kinetics are then solved using a parallel algorithm based on Douglas-Gunn that handles the irregular 3D geometry of a neuron; these kinetics are coupled to NEURON's 1D mechanisms for ion channels, synapses, pumps, and so forth. The 3D domain may cover the entire cell or selected regions of interest. Simulations with dendritic spines and of the soma reveal details of dynamics that would be missed in a pure 1D simulation. We describe and validate the methods and discuss their performance.
神经元活动是电生理学和化学生理学共同作用的结果。为了进行电生理模拟,神经元可以很好地表示为由相连圆柱体组成的树状结构。只要空间尺度大于圆柱体的直径且具有径向对称性,这种表示对于其化学生理学的一维模拟也是合适的。当不满足这些标准时,例如存在波曲率、树突棘或胞体附近的扩散时,就需要进行更高维度的模拟来准确捕捉动力学。我们开发了一种解决方案,以实现对神经元和网络模型中细胞内三维区域的反应扩散动力学进行高效的有限体积法模拟,并在NEURON模拟器中提供了一个实现方案。CTNG三维重建算法的加速版本将适合基于离子通道模拟的形态转化为一致的三维体素化区域。然后使用基于道格拉斯 - 冈恩的并行算法求解动力学,该算法处理神经元不规则的三维几何形状;这些动力学与NEURON用于离子通道、突触、泵等的一维机制相耦合。三维域可以覆盖整个细胞或选定的感兴趣区域。对树突棘和胞体的模拟揭示了纯一维模拟中会遗漏的动力学细节。我们描述并验证了这些方法,并讨论了它们的性能。