Computational Physics Laboratory, Ioffe Institute, Saint Petersburg, Russia.
Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russia.
PLoS One. 2019 Mar 15;14(3):e0213904. doi: 10.1371/journal.pone.0213904. eCollection 2019.
Despite big experimental data on the phenomena and mechanisms of the generation of ictal and interictal discharges (IDs and IIDs), mathematical models that can describe the synaptic interactions of neurons and the ionic dynamics in biophysical detail are not well-established. Based on experimental recordings of combined hippocampal-entorhinal cortex slices from rats in a high-potassium and a low-magnesium solution containing 4-aminopyridine as well as previous observations of similar experimental models, this type of mathematical model has been developed. The model describes neuronal excitation through the application of the conductance-based refractory density approach for three neuronal populations: two populations of glutamatergic neurons with hyperpolarizing and depolarizing GABAergic synapses and one GABAergic population. The ionic dynamics account for the contributions of voltage-gated and synaptic channels, active and passive transporters, and diffusion. The relatively slow dynamics of potassium, chloride, and sodium ion concentrations determine the transitions from pure GABAergic IIDs to IDs and GABA-glutamatergic IIDs. The model reproduces different types of IIDs, including those initiated by interneurons; repetitive IDs; tonic and bursting modes of an ID composed of clustered IID-like events. The simulations revealed contributions from different ionic channels to the ion concentration dynamics before and during ID generation. The proposed model is a step forward to an optimal mathematical description of the mechanisms of epileptic discharges.
尽管有大量关于癫痫发作和发作间期放电（IDs 和 IIDs）现象和机制的实验数据，但能够详细描述神经元突触相互作用和离子动力学的数学模型尚未得到很好的建立。本模型基于在含有 4-氨基吡啶的高钾和低镁溶液中对大鼠海马-内嗅皮层联合切片的实验记录以及类似实验模型的先前观察结果而开发。该模型通过应用基于电导率的不应期密度方法来描述神经元的兴奋，涉及三种神经元群体：具有去极化和超极化 GABA 能突触的两种谷氨酸能神经元群体和一种 GABA 能神经元群体。离子动力学考虑了电压门控和突触通道、主动和被动转运体以及扩散的贡献。钾、氯和钠离子浓度的相对缓慢动力学决定了从纯 GABA 能 IIDs 到 IDs 和 GABA-谷氨酸能 IIDs 的转变。该模型再现了不同类型的 IIDs，包括由中间神经元引发的 IIDs、重复 IDs、由簇集的 IID 样事件组成的 ID 的紧张和爆发模式。模拟揭示了在 ID 产生之前和期间，不同离子通道对离子浓度动力学的贡献。所提出的模型是朝着优化癫痫放电机制的数学描述迈出的一步。
