A New Therapy of Epilepsy by Enhancing Inhibition of Gabaergic Neurons

Epilepsy is a neural disorder related to the imbalance between inhibition and excitation of the brain. Enhancement of inhibition can be used to treat epilepsy. Here, we discovered that the inhibition of cortical GABAergic neurons was potentiated after high-frequency optogenetic activation but not low-frequency. GABAergic neurons were activated chemogenetically to fire at high frequency, suppressing spontaneous neuronal activities and auditory responses in the long term during the 2-hour recording. We produced chronic epileptic mice after the intrahippocampal injection of kainic acid. Viral vectors of hM3Dq were delivered intravenously to infect the inhibitory neurons in our epileptic mice. We developed an artificial-intelligent program to objectively detect each convulsive seizure before, during, and after the chemogenetic treatment. Administration of clozapine-N-oxide suppressed the epileptic activities during and even more the week after drug application. The results demonstrate a novel gene therapy for chronic epilepsy by enhancing the inhibition of global GABAergic neurons.