On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy

Abstract

Temporal lobe epilepsy is the most common type of epilepsy in adults, is often medically refractory, and due to broad actions and long-time scales, current systemic treatments have major negative side-effects. However, temporal lobe seizures tend to arise from discrete regions before overt clinical behaviour, making temporally and spatially specific treatment theoretically possible. Here we report the arrest of spontaneous seizures using a real-time, closed-loop, response system and in vivo optogenetics in a mouse model of temporal lobe epilepsy. Either optogenetic inhibition of excitatory principal cells, or activation of a subpopulation of GABAergic cells representing <5% of hippocampal neurons, stops seizures rapidly upon light application. These results demonstrate that spontaneous temporal lobe seizures can be detected and terminated by modulating specific cell populations in a spatially restricted manner. A clinical approach built on these principles may overcome many of the side-effects of currently available treatment options. Temporal lobe epilepsy in adults does not always respond to treatment. Krook-Magnuson and colleagues use optogenetics to inhibit and activate excitatory and inhibitory neurons, respectively, in a mouse model of temporal lobe epilepsy, and find that they can stop seizures on a moment-to-moment basis.