Astrocyte-mediated neuronal irregularities and dynamics: the complexity of the tripartite synapse

Abstract

Despite significant advancements in recent decades, gaining a comprehensive understanding of brain computations remains a significant challenge in neuroscience. Using computational models is crucial for unraveling this complex phenomenon and is equally indispensable for studying neurological disorders. This endeavor has created many neuronal models that capture brain dynamics at various scales and complexities. However, most existing models do not account for the potential influence of glial cells, particularly astrocytes, on neuronal physiology. This gap persists even with the emerging evidence indicating their critical role in regulating neural network activity, plasticity, and even neurological pathologies. To address this gap, some works proposed models that include neuron–glia interactions. Also, while some literature focuses on sophisticated models of neuron–glia interactions that mimic the complexity of physiological phenomena, there are also existing works that propose simplified models of neural–glial ensembles. Building upon these efforts, we aimed to contribute further to the field by proposing a simplified tripartite synapse model that encompasses the presynaptic neuron, postsynaptic neuron, and astrocyte. We defined the tripartite synapse model based on the Adaptive Exponential Integrate-and-Fire neuron model and a simplified scheme of the astrocyte model previously proposed by Postnov. Through our simulations, we demonstrated how astrocytes can influence neuronal firing behavior by sequentially activating and deactivating different pathways within the tripartite synapse. This modulation by astrocytes can shape neuronal behavior and introduce irregularities in the firing patterns of both presynaptic and postsynaptic neurons through the introduction of new pathways and configurations of relevant parameters.