Centre for Integrative Neuroplasticity, University of Oslo, Oslo, Norway.
Department of Physics, University of Oslo, Oslo, Norway.
PLoS Comput Biol. 2020 Apr 29;16(4):e1007661. doi: 10.1371/journal.pcbi.1007661. eCollection 2020 Apr.
In most neuronal models, ion concentrations are assumed to be constant, and effects of concentration variations on ionic reversal potentials, or of ionic diffusion on electrical potentials are not accounted for. Here, we present the electrodiffusive Pinsky-Rinzel (edPR) model, which we believe is the first multicompartmental neuron model that accounts for electrodiffusive ion concentration dynamics in a way that ensures a biophysically consistent relationship between ion concentrations, electrical charge, and electrical potentials in both the intra- and extracellular space. The edPR model is an expanded version of the two-compartment Pinsky-Rinzel (PR) model of a hippocampal CA3 neuron. Unlike the PR model, the edPR model includes homeostatic mechanisms and ion-specific leakage currents, and keeps track of all ion concentrations (Na+, K+, Ca2+, and Cl-), electrical potentials, and electrical conductivities in the intra- and extracellular space. The edPR model reproduces the membrane potential dynamics of the PR model for moderate firing activity. For higher activity levels, or when homeostatic mechanisms are impaired, the homeostatic mechanisms fail in maintaining ion concentrations close to baseline, and the edPR model diverges from the PR model as it accounts for effects of concentration changes on neuronal firing. We envision that the edPR model will be useful for the field in three main ways. Firstly, as it relaxes commonly made modeling assumptions, the edPR model can be used to test the validity of these assumptions under various firing conditions, as we show here for a few selected cases. Secondly, the edPR model should supplement the PR model when simulating scenarios where ion concentrations are expected to vary over time. Thirdly, being applicable to conditions with failed homeostasis, the edPR model opens up for simulating a range of pathological conditions, such as spreading depression or epilepsy.
在大多数神经元模型中，离子浓度被假定为恒定的，并且浓度变化对离子反转电位的影响，或者离子扩散对电势能的影响都没有被考虑到。在这里，我们提出了电扩散的 Pinsky-Rinzel（edPR）模型，我们相信这是第一个多室神经元模型，它以一种确保离子浓度、电荷和内外空间电势能之间具有生物物理一致性的方式来考虑电扩散离子浓度动力学。edPR 模型是一个扩展的两室 Pinsky-Rinzel（PR）海马 CA3 神经元模型。与 PR 模型不同，edPR 模型包括了自动调节机制和离子特异性泄漏电流，并跟踪内外空间中的所有离子浓度（Na+、K+、Ca2+和 Cl-）、电势能和电导率。edPR 模型为中等放电活动重现了 PR 模型的膜电位动力学。对于更高的活动水平，或者当自动调节机制受损时，自动调节机制无法将离子浓度维持在基线附近，并且 edPR 模型由于考虑了浓度变化对神经元放电的影响而与 PR 模型分道扬镳。我们设想 edPR 模型将以三种主要方式对该领域有用。首先，由于它放宽了常见的建模假设，因此可以根据各种放电情况来测试这些假设的有效性，就像我们在这里针对一些选定的情况所展示的那样。其次，当模拟预计离子浓度随时间变化的情况时，edPR 模型应该补充 PR 模型。第三，由于适用于自动调节失败的情况，edPR 模型为模拟一系列病理状况（如扩散性抑制或癫痫）开辟了道路。
