A computational study on the role of glutamate and NMDA receptors on cortical spreading depression using a multidomain electrodiffusion model.

使用多域电扩散模型对谷氨酸和 NMDA 受体在皮质扩散抑制中的作用进行计算研究。

• 影响指数: 4.779
• 发表时间: 12 2019
• 来源期刊: PLoS Comput Biol
• DOI: 10.1371/journal.pcbi.1007455
• PMID: 31790388
• 文章类型: Journal Article
• 作者列表: Tuttle A,Riera Diaz J,Mori Y

Mesh: Animals; Brain / metabolism; Computational Biology; Computer Simulation; Cortical Spreading Depression / physiology; Glutamic Acid / metabolism; Humans; Ion Channels / metabolism; Models, Neurological; Neurons / metabolism; Nonlinear Dynamics; Potassium / metabolism; Receptors, N-Methyl-D-Aspartate / metabolism; Sodium Channels / metabolism

Abstract

Cortical spreading depression (SD) is a spreading disruption of ionic homeostasis in the brain during which neurons experience complete and prolonged depolarizations. SD is the basis of migraine aura and is increasingly associated with many other brain pathologies. Here, we study the role of glutamate and NMDA receptor dynamics in the context of an ionic electrodiffusion model. We perform simulations in one (1D) and two (2D) spatial dimension. Our 1D simulations reproduce the \"inverted saddle\" shape of the extracellular voltage signal for the first time. Our simulations suggest that SD propagation depends on two overlapping mechanisms; one dependent on extracellular glutamate diffusion and NMDA receptors and the other dependent on extracellular potassium diffusion and persistent sodium channel conductance. In 2D simulations, we study the dynamics of spiral waves. We study the properties of the spiral waves in relation to the planar 1D wave, and also compute the energy expenditure associated with the recurrent SD spirals.

摘要

皮质扩散抑制（SD）是大脑中离子稳态的扩散破坏，在此期间神经元经历完全和长时间的去极化。SD是偏头痛先兆的基础，并且与许多其他脑部病理越来越相关。这里,我们在离子电扩散模型的背景下研究谷氨酸和NMDA受体动力学的作用。我们在一个（1D）和两个（2D）空间维度进行模拟。我们的一维模拟首次再现了细胞外电压信号的“倒鞍形”。我们的模拟表明，SD传播取决于两个重叠的机制；一个依赖于细胞外谷氨酸扩散和NMDA受体，另一个依赖于细胞外钾扩散和持续的钠通道电导。在2D模拟中，我们研究螺旋波的动力学。我们研究了螺旋波与平面一维波的关系，并计算与复发性SD螺旋相关的能量消耗。