Compensatory Mechanisms Modulate The Neuronal Excitability In A Kainic Acid-Induced Epilepsy Mouse Model

Epilepsy is a chronic and recurrent episode of transient brain dysfunction,characterized by super-synchronous abnormal discharge of neurons in the brain.Its pathogenesis is complex and unclear,and the incidence rate is increasing year by year.Epileptic discharge is closely related to neurotransmission.Excitatory and inhibitory neurotransmitters maintain a state of equilibrium under normal conditions.Excessive excitatory neurotransmitter or reduced inhibitory transmitter results in imbalance of neuronal excitation,andepileptic discharge from overexcited neurons.However,the intrinsic detailed mechanism is still unclear.In this study,we are elucidating the possible mechanisms of neuronal excitability during epileptic seizures.Hopefully this study will provide evaluable clues for potential treatment and diagnosis of the disease.In this study,we used a kainic acid(KA)-induced epilepsy mouse model to investigate the regulatory mechanisms in epilepsy.The extent of seizure severity was evaluated according to Racine’s scale and the mice were subjected to EEG recording·To investigate the activity change of ion channels in the brain,the action potentials,spontaneous excitability(sEPSCs)and inhibitory(sIPSCs)synaptic currents,and tonic inhibitory currents were recorded in the mouse brain slices at different period after KA injection by using electrophysiological patch clamp technique.The results indicates that the excitability of cortical neurons in epileptic mice experienced a complex process from increasing to decreasing.Through further research,we found that the main cause of this decrease in neuronal excitability is not the change of neuronal synaptic activity,but the excessive activation of glial cells,releasing the inhibitory neurotransmitter GABA and leading to enhanced tonic inhibition.Immunofluorescence staining also confirmed that levels of activated astrocytes and inhibitory neurotransmitters were significantly elevated in the cortex of KA-induced epilepsy mice.We hypothesize that the elevated tonic inhibition after seizures in mice may be a self-protective mechanism of the nervous system to counteract the toxic neuronal over-excitation.This study provides useful clues to further elucidate the pathological mechanisms of neuronal activity in the pathogenesis of epilepsy,and provide a potential therapeutic target for the treatment of epilepsy.