Modeling Neuroplasticity in Cortical and Hippocampal Microcircuits: Toward Improved Understanding of Epilepsy

This study was conducted within the framework of the GALVANI project, which aims to develop computational and experimental tools to optimize non-invasive brain stimulation for drug-resistant epilepsy (DRE). The work focused on integrating biologically realistic neuroplasticity mechanisms into detailed models of hippocampal and neocortical microcircuits to examine how synaptic plasticity contributes to epileptiform dynamics and affects transcranial electrical stimulation (tES). Two calcium-dependent plasticity models (Shouval and Brunel) were considered and combined into a novel Hybrid model merging Shouval’s continuous calcium dependence with Brunel’s stabilizing bistability. Validation in small networks reproduced long-term potentiation (LTP), long-term depression (LTD), and triphasic spike-timing-dependent plasticity (STDP), showing how parameter shifts can bias potentiation. The models were then applied to large-scale hippocampal CA1 and neocortical networks. To simulate epileptiform activity, cellular and network parameters were adjusted to induce a hyperexcitable state generating interictal epileptiform spikes (IESs). In the hippocampal model, Shouval’s plasticity increased pyramidal firing rates (FRs) and high-frequency activity, leading to excessive excitation, whereas the Hybrid model produced moderate FR increases and preserved IES morphology. In the neocortical model, hybrid plasticity similarly enhanced excitability while maintaining rhythmic organization. Preliminary tES simulations showed cathodal tDCS induced mild potentiation, whereas anodal tDCS caused slight depression. These findings show that calcium-dependent plasticity shapes network excitability and modulates tES effects, supporting the GALVANI project’s goal of developing personalized neuromodulation strategies for epilepsy.