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.
Highlights
Neural activity in the brain results from an interplay between neuronal excitation and inhibition and is subjected to the supply of nutrients by the cerebral blood flow
We have introduced a novel neuron–astrocyte mass model, which combines two previously studied models [29, 30] by bidirectional neuron–astrocyte coupling based on astrocytic uptake-mediated modulations of extracellular glutamate and GABA concentrations and their effect on neural activity in agreement with experimental observations [10, 37, 44, 45]
Based on the interpretation of the aggregated—yet biophysically significant parameters of our model—we have reproduced in silico both glutamate and GABA uptake deficiency in astrocytes and illustrated by numerical simulations the different types of change in the neural activity resulting from such deficiency
Summary
Neural activity in the brain results from an interplay between neuronal excitation and inhibition and is subjected to the supply of nutrients by the cerebral blood flow. A novel computational model based on the neural mass approach that focuses on astrocyte dynamics at the mesoscopic scale has recently been proposed [30] This model links the LFP signal representative of neural activity measured by intracranial EEG to the cerebral blood flow dynamics measured by laser doppler recordings of astrocyte activity. We identify three possible neural regimes in the presence of deficiency of astrocytic glutamate uptake, respectively, consistent with reduced activity, transient or permanent hyperexcitability Such a spectrum of responses is substantiated by the analysis of the dynamical structure of the model, which allows us to derive explicit conditions on the parameters involved in the astrocytic feedback corresponding to each type of regime and put emphasis on the delicate balance between neuronal excitation and inhibition and its sensitivity to extracellular concentrations of neurotransmitters
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