Active enhancement of synapse driven depolarization of perisynaptic astrocytic processes

Abstract

AbstractElectrophysiological properties underlie the fundamental mechanisms of the brain. Although astrocytes have typically been considered not electrically excitable, recent studies have shown depolarization of astrocytes induced by local extracellular potassium changes caused by neuronal activity. Interestingly, astro-cytic depolarization is only induced within the periphery of the astrocyte, where astrocytes contact neurons. This depolarization affects the brain’s information processing, as depolarization alters astrocyte functionality and neurotransmit-ter dynamics. However, specific mechanisms causing astrocytic depolarization have remained unknown due to the limitations of experimental techniques. Here, we construct a computational whole-cell astrocyte model containing experimen-tally verified astrocytic channels relevant to depolarization. Using our model, we suggest that previously reported potassium channels alone are insufficient for astrocyte depolarization and additional mechanisms are required. Our sim-ulations show that NMDARs contribute to this depolarization by cooperating with Kir 4.1 to actively enhance extracellular potassium concentration and, thus, sustain depolarization.