Verisokin Andrey Yu, Verveyko Darya V, Postnov Dmitry E, Brazhe Alexey R
Department of Theoretical Physics, Kursk State University, Kursk, Russia.
Department of Optics and Biophotonics, Saratov State University, Saratov, Russia.
Front Cell Neurosci. 2021 Mar 5;15:645068. doi: 10.3389/fncel.2021.645068. eCollection 2021.
Neuronal firing and neuron-to-neuron synaptic wiring are currently widely described as orchestrated by astrocytes-elaborately ramified glial cells tiling the cortical and hippocampal space into non-overlapping domains, each covering hundreds of individual dendrites and hundreds thousands synapses. A key component to astrocytic signaling is the dynamics of cytosolic Ca which displays multiscale spatiotemporal patterns from short confined elemental Ca events (puffs) to Ca waves expanding through many cells. Here, we synthesize the current understanding of astrocyte morphology, coupling local synaptic activity to astrocytic Ca in perisynaptic astrocytic processes and morphology-defined mechanisms of Ca regulation in a distributed model. To this end, we build simplified realistic data-driven spatial network templates and compile model equations as defined by local cell morphology. The input to the model is spatially uncorrelated stochastic synaptic activity. The proposed modeling approach is validated by statistics of simulated Ca transients at a single cell level. In multicellular templates we observe regular sequences of cell entrainment in Ca waves, as a result of interplay between stochastic input and morphology variability between individual astrocytes. Our approach adds spatial dimension to the existing astrocyte models by employment of realistic morphology while retaining enough flexibility and scalability to be embedded in multiscale heterocellular models of neural tissue. We conclude that the proposed approach provides a useful description of neuron-driven Ca-activity in the astrocyte syncytium.
目前，神经元放电以及神经元与神经元之间的突触连接广泛被描述为由星形胶质细胞精心编排，星形胶质细胞是一种高度分支的神经胶质细胞，它们将皮质和海马空间划分成互不重叠的区域，每个区域覆盖数百个单个树突和数十万突触。星形胶质细胞信号传导的一个关键组成部分是胞质钙的动态变化，其表现出多尺度的时空模式，从短暂局限的基本钙事件（钙瞬变）到扩展至许多细胞的钙波。在这里，我们在一个分布式模型中综合了当前对星形胶质细胞形态、将局部突触活动与突触周围星形胶质细胞过程中的星形胶质细胞钙耦合以及钙调节的形态学定义机制的理解。为此，我们构建了简化的、基于现实数据驱动的空间网络模板，并根据局部细胞形态编译模型方程。模型的输入是空间上不相关的随机突触活动。所提出的建模方法通过单细胞水平模拟钙瞬变的统计数据得到验证。在多细胞模板中，由于随机输入与单个星形胶质细胞之间形态学变异性的相互作用，我们观察到钙波中细胞夹带的规则序列。我们的方法通过采用现实的形态学为现有的星形胶质细胞模型增加了空间维度，同时保留了足够的灵活性和可扩展性，以便嵌入神经组织的多尺度异质细胞模型中。我们得出结论，所提出的方法为星形胶质细胞合体中神经元驱动的钙活动提供了有用的描述。
