A Theoretical Study on the Role of Astrocytic Activity in Neuronal Hyperexcitability by a Novel Neuron-Glia Mass Model

Abstract

Recent experimental evidence on the clustering of glutamate and GABA transporters on astrocytic processes surrounding synaptic terminals pose the question of the functional relevance of the astrocytes in the regulation of neural activity. In this perspective, we introduce a new computational model that embeds recent findings on neuron–astrocyte coupling at the mesoscopic scale intra- and inter-layer local neural circuits. The model consists of a mass model for the neural compartment and an astrocyte compartment which controls dynamics of extracellular glutamate and GABA concentrations. By arguments based on bifurcation theory, we use the model to study the impact of deficiency of astrocytic glutamate and GABA uptakes on neural activity. While deficient astrocytic GABA uptake naturally results in increased neuronal inhibition, which in turn results in a decreased neuronal firing, deficient glutamate uptake by astrocytes may either decrease or increase neuronal firing either transiently or permanently. Given the relevance of neuronal hyperexcitability (or lack thereof) in the brain pathophysiology, we provide biophysical conditions for the onset identifying different physiologically relevant regimes of operation for astrocytic uptake transporters.