A new pathway for controlling absence seizures by reducing GABA uptake from astrocytes: a dynamical perspective

Abstract

Modeling studies associated with absence epilepsy often consider neural circuits and neglect the critical involvement of glial cells. Recently, the view that astrocytes are new targets for the treatment of epilepsy has received increasing attention. Based on the established basal ganglia-corticothalamic (BGCT) mean-field model involving glutamate (GLU) dynamics in the extracellular space of cerebral cortex, by introducing γ-aminobutyric acid (GABA) dynamical processes, we further extend the model and explore the effectiveness of inhibiting the GABA uptake from cortical astrocytes (V_gai) in controlling seizures induced by different triggers. The results show that reducing V_gai can control seizures to a certain extent, regardless of the neural triggers with two types of abnormal feedforward inhibition or the astrocytic triggers with insufficient glutamate uptake from astrocytes. Although no uniform conclusions are achieved by comparing the above measure for the control of seizures caused by different triggers, it is worth noting that the setting of the initial condition greatly affects the control rate of spike wave discharges (SWDs). Appropriate selection of initial values can make reducing GABA uptake from astrocytes more effective in eliminating SWDs. Our results provide a theoretical basis for the treatment of epilepsy by targeting astrocytes from a dynamical perspective.