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

2019; Public Library of Science; Volume: 15; Issue: 12 Linguagem: Inglês

10.1371/journal.pcbi.1007455

1553-7358

Austin Tuttle, Jorge Riera, Yoichiro Mori,

Neural dynamics and brain function

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.