IEEE/ACM Trans Comput Biol Bioinform. 2019 May-Jun;16(3):1007-1019. doi: 10.1109/TCBB.2017.2756930. Epub 2017 Sep 26.
The intra-cellular calcium signaling pathways of a neuron depends on both biochemical reactions and diffusions. Some quasi-isolated compartments (e.g., spines) are so small and calcium concentrations are so low that one extra molecule diffusing in by chance can make a nontrivial difference in concentration (percentage-wise). These rare events can affect dynamics discretely in such a way that they cannot be evaluated by a deterministic and continuous simulation. Stochastic models of such a system provide a more detailed understanding of these systems than existing deterministic models because they capture their behavior at a molecular level. Our research focuses on the development of a high performance parallel discrete event simulation environment, Neuron Time Warp (NTW), which is intended for use in the parallel simulation of stochastic reaction-diffusion systems such as intra-calcium signaling. NTW is integrated with NEURON, a simulator which is widely used within the neuroscience community. We simulate two models, a calcium buffer and a calcium wave model. The calcium buffer model is employed in order to verify the correctness and performance of NTW by comparing it to a sequential deterministic simulation in NEURON. We also derived a discrete event calcium wave model from a deterministic model using the stochastic $\text{IP}_{3}\text{R}$IP3R structure.
神经元的细胞内钙信号通路既依赖于生化反应,也依赖于扩散。一些准隔离的隔室(例如,棘突)非常小,钙离子浓度非常低,以至于一个偶然扩散进来的额外分子可以使浓度产生相当大的差异(按百分比计算)。这些罕见的事件可以以离散的方式影响动力学,以至于它们不能通过确定性和连续的模拟来评估。这种系统的随机模型比现有的确定性模型提供了对这些系统更详细的理解,因为它们在分子水平上捕获了它们的行为。我们的研究重点是开发高性能并行离散事件模拟环境 Neuron Time Warp (NTW),该环境旨在用于对钙信号等随机反应扩散系统进行并行模拟。NTW 与神经科学社区广泛使用的模拟器 NEURON 集成在一起。我们模拟了两个模型,一个钙缓冲器模型和一个钙波模型。钙缓冲器模型用于通过将其与 NEURON 中的顺序确定性模拟进行比较来验证 NTW 的正确性和性能。我们还使用随机的 $\text{IP}_{3}\text{R}$-IP3R 结构从确定性模型推导出离散事件钙波模型。