Transition behavior of the seizure dynamics modulated by the astrocyte inositol triphosphate noise.

Abstract

Epilepsy is a neurological disorder with recurrent seizures, which convey complex dynamical characteristics including chaos and randomness. Until now, the underlying mechanism has not been fully elucidated, especially the bistable property beneath the epileptic random induction phenomena in certain conditions. Inspired by the recent finding that astrocyte GTPase-activating protein (G-protein)-coupled receptors could be involved in stochastic epileptic seizures, we proposed a neuron-astrocyte network model, incorporating the noise of the astrocytic second messenger, inositol triphosphate (IP3) that is modulated by G-protein-coupled receptor activation. Based on this model, we have statistically analyzed the transitions of epileptic seizures by performing repeatable simulation trials. Our simulation results show that the increase in the IP3 noise intensity induces depolarization-block epileptic seizures together with an increase in neuronal firing frequency, consistent with corresponding experiments. Meanwhile, the bistable states of the seizure dynamics were present under certain noise intensities, during which the neuronal firing pattern switches between regular sparse spiking and epileptic seizure states. This random presence of epileptic seizures is absent when the noise intensity continues to increase, accompanying with an increase in the epileptic depolarization block duration. The simulation results also shed light on the fact that calcium signals in astrocytes play significant roles in the pattern formations of the epileptic seizure. Our results provide a potential pathway for understanding the epileptic randomness in certain conditions.