Striatum is the potential target for treating absence epilepsy: a theoretical evidence

Abstract

The output of the basal ganglia to the corticothalamic system plays an important role in regulating absence seizures. Inspired by experiments, we systematically study the crucial roles of two newly identified direct inhibitory striatal-cortical projections that project from the striatal D1 nucleus (SD1) and striatal D2 nucleus (SD2) to the cerebral cortex, in controlling absence seizures. Through computational simulation, we observe that typical 2–4 Hz spike and wave discharges (SWDs) can be induced through the pathological mechanism of cortical circuits, and both enhancing the inhibitory coupling weight on the striatal-cortical projections and improving the discharge activation level of striatal populations can effectively control typical SWDs. Furthermore, typical SWDs can be suppressed by appropriately adjusting several input projections directly related to the striatum, through regulating the activation level of striatal populations. Interestingly, several indirect striatum-related basal ganglia projections also have significant effects on the inhibition of typical SWDs, through the direct inhibitory striatal-cortical projections. Both the unidirectional control mode and bidirectional control mode for typical SWDs exist in our modified model. Importantly, the enhancement of coupling strengths on inhibitory striatal-cortical projections is beneficial for suppressing SWDs and may play a decisive regulatory role in the formation of control modes. Therefore, our study suggests that striatum may be potential effective targets for the treatment of absence seizures, through two newly identified direct inhibitory striatal-cortical projections. Interestingly, we find that external stimuli simultaneously targeting the striatum and another basal ganglia nucleus have a better control effect on SWDs than targeting a single basal ganglia nucleus, and the obtained results provide testable hypotheses for future experiments.