Dynamical regulation of epileptiform discharges caused by abnormal astrocyte function with optogenetic stimulation

Abstract

A simple network model consisting of a pyramidal neuron, an interneuron, and an astrocyte is constructed to simulate epileptiform discharges, focusing on the role of the interneuron in the pathological state. Simulation results show that with the change of the parameters related to abnormal glutamate degradation, the system can be transformed from bursting discharges or subthreshold oscillations to seizure-like discharges containing depolarization block. Meanwhile, the proposal of optogenetics has made it possible to target specific cells to modulate seizures, however, discoveries remain to be made regarding the specific effects limited by light mechanisms, stimulation patterns, and other factors. Hence, based on the constructed model, firstly, the experimental phenomenon that different types of light mechanisms are required to target the interneuron to control seizures under different situations is verified, and further, the effect of blue light targeting the astrocyte on seizure thresholds is revealed. The results demonstrate that the choice of stimulation frequency for seizure control varies in different situations, but the pulse width must be larger to be more conducive to control. In particular, the inhibitory photostimulation may change bursting discharges into spike discharges or subthreshold oscillations, in addition to eliminating the depolarization block part of the bursting discharges. Due to the slow-scale variation of calcium dynamics, stimulation with the same duty cycle does not have a consistent effect on thresholds for the appearance of epileptiform discharges. More importantly, by means of dynamical changes in the calcium signal near the bifurcation point from oscillation to resting, the effect of different stimulation patterns on the onset threshold can be explained. Our results may provide theoretical insight for the application of optogenetics in epileptic disorders caused by abnormal astrocyte function.