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.
Bibliographical noteFunding Information:
We would like to thank the entire Soltesz lab, especially Judit Varga, Kyle Pendergast, Rose Zhu, Sean Lew, Dhrumil Vyas, Chris Krook-Magnuson, Anh Bui, Hannah Kim, and Csaba Varga for technical support. We thank Hongkui Zeng and the Allen Brain Institute for the Ai32 transgenic mice, Dr Karl Deisseroth for support, Dr Steven Ross for the loan of the Nikon FN-1 Eclipse microscope, and Dr Christine Gall and Conor Cox for assistance with imaging. This work was supported by the US National Institutes of Health grant NS074702 (to I.S.), the Epilepsy Foundation (to C.A.), and the George E. Hewitt Foundation for Medical Research (to E.K.-M.).