Neural synchronization is fundamental to brain function and, when it becomes excessive, underlies pathological conditions such as epilepsy. Among brain regions, the temporal lobes, and the hippocampus in particular, exhibit the highest epileptogenic potential, with mesial temporal lobe epilepsy representing the most prevalent form of the condition in humans. Within the hippocampus, extracellular potassium dynamics are central to non-synaptic epileptiform activity, and astrocytic potassium buffering mechanisms have emerged as key regulators of network excitability. Yet the specific contributions of astrocytic gap-junction coupling and potassium spatial buffering to neuronal synchronization across different spatial scales remain poorly understood. To address this gap, we developed a microcircuit biophysical model consisting of two astrocyte-neuron modules, each comprising one astrocyte coupled to five neurons. Astrocyte-neuron interactions are mediated exclusively through shared extracellular potassium dynamics. Using a reduced astrocyte model that captures both local membrane and syncytial potassium buffering, we systematically investigated how astrocytic potassium handling shapes neuronal activity patterns and inter-module synchronization. Our results demonstrate that astrocytes prevent the emergence of pathological states - such as sustained ictal activity and depolarization block, by stabilizing extracellular potassium levels. Furthermore, we show that astrocytic gap-junction coupling strength critically regulates phase synchronization between neuronal modules: stronger coupling promotes inter-module synchrony under physiological conditions, whereas impaired astrocytic function drives networks toward pathological hypersynchronization when extracellular potassium is elevated. These findings support the hypothesis that astrocytic networks impose modularity on hippocampal neuronal assemblies, and suggest that astrocytic connexins may represent a relevant therapeutic target in epilepsy and other disorders characterized by aberrant neural synchronization.
Cafiso, M., Casagrande, G., Angiolelli, M., Paradisi, P., Sorrentino, P., Depannemaecker, D.
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