Modeling of Entorhinal cortex and simulation of epileptic activity: Insights into the role of inhibition-related parameters

This paper describes a macroscopic neurophysiologically relevant model of the entorhinal cortex (EC), a brain structure largely involved in human mesio-temporal lobe epilepsy. This model is intervalidated in the experimental framework of ictogenesis animal model (isolated guinea-pig brain perfused with bicuculline). Using sensitivity and stability analysis, an investigation of model parameters related to GABA neurotransmission (recognized to be involved in epileptic activity generation) was performed. Based on spectral and statistical features, simulated signals generated from the model for multiple GABAergic inhibition-related parameter values were classified into eight classes of activity. Simulated activities showed striking agreement (in terms of realism) with typical epileptic activities identified in field potential recordings performed in the experimental model. From this combined computational/experimental approach, hypotheses are suggested about the role of different types of GABAergic neurotransmission in the generation of epileptic activities in EC.