Epileptic seizures are the manifestation of hypersynchronous and excessive neuronal excitation. While the glutamatergic and GABAergic neurons play major roles in shaping fast neuronal excitation/inhibition homeostasis, it is well illustrated that astrocytes profoundly regulate neuronal excitation by controlling glutamate, GABA, cannabinoids, adenosine and concentration of K+ around neurons. However, little is known whether microglia take part in the regulation of acute neuronal excitation and ongoing epileptic behaviors. We proposed that if microglia are innately ready to respond to epileptic overexcitation, depletion of microglia might alter neuronal excitability and severity of acute epileptic seizures. We found that microglia depletion by PLX3397, an inhibitor of CSF1R, exacerbates seizure severity and excitotoxicity-induced neuronal degeneration, indicating that microglia are rapidly responsive to the change of excitation/inhibition homeostasis and participate in the protection of neurons from overexcitation.

TRESK channel contributes to depolarizationinduced shunting inhibition and modulates epileptic seizuresGraphical abstract Highlights d A sustained seizure-like depolarization induces a transient shunting inhibition d This non-synaptic form of short-term plasticity contributes to seizure termination d TRESK, a subtype of K + channels, contributes to this shunting inhibition d Activating TRESK shortens seizure duration and prolongs postictal depression