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. 2020 Apr 10;15(4):e0230787. doi: 10.1371/journal.pone.0230787. eCollection 2020.
The mechanisms of epileptic discharge generation and spread are not yet fully known. A recently proposed simple biophysical model of interictal and ictal discharges, Epileptor-2, reproduces well the main features of neuronal excitation and ionic dynamics during discharge generation. In order to distinguish between two hypothesized mechanisms of discharge propagation, we extend the model to the case of two-dimensional propagation along the cortical neural tissue. The first mechanism is based on extracellular potassium diffusion, and the second is the propagation of spikes and postsynaptic signals along axons and dendrites. Our simulations show that potassium diffusion is too slow to reproduce an experimentally observed speed of ictal wavefront propagation (tenths of mm/s). By contrast, the synaptic mechanism predicts well the speed and synchronization of the pre-ictal bursts before the ictal front and the afterdischarges in the ictal core. Though this fact diminishes the role of diffusion and electrodiffusion, the model nevertheless highlights the role of potassium extrusion during neuronal excitation, which provides a positive feedback that changes at the ictal wavefront the balance of excitation versus inhibition in favor of excitation. This finding may help to find a target for a treatment to prevent seizure propagation.
癫痫放电产生和传播的机制尚不完全清楚。最近提出的一种简单的癫痫发作间期和发作期放电的生物物理模型 Epileptor-2，很好地再现了放电产生过程中神经元兴奋和离子动力学的主要特征。为了区分两种假设的放电传播机制，我们将模型扩展到沿皮质神经组织二维传播的情况。第一种机制基于细胞外钾扩散，第二种机制是尖峰和突触后信号沿着轴突和树突传播。我们的模拟表明，钾扩散速度太慢，无法重现实验观察到的癫痫波阵面传播速度（十分之几毫米/秒）。相比之下，突触机制很好地预测了癫痫发作前沿前的预癫痫爆发和癫痫核心中的后放电的速度和同步性。尽管这一事实降低了扩散和电扩散的作用，但该模型仍强调了神经元兴奋过程中钾外排的作用，这提供了一个正反馈，在癫痫波阵面改变兴奋与抑制之间的平衡，有利于兴奋。这一发现可能有助于找到一种治疗方法的靶点，以防止癫痫发作的传播。
