title: 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.
authors: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1280, USA. ekrookma@uci.edu
authors: Esther
authors: E
authors: Krook-Magnuson
authors: Caren
authors: C
authors: Armstrong
authors: Mikko
authors: M
authors: Oijala
authors: Ivan
authors: I
authors: Soltesz
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D000075402:Channelrhodopsins; D003199:Computer Systems; D004195:Disease Models, Animal; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D059330:GABAergic Neurons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D025602:Halorhodopsins / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D019426:Integrases / Q000378:metabolism; D008027:Light; D051379:Mice; D062308:Optogenetics / Q000379:methods*; D012640:Seizures / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D000075402:Channelrhodopsins; D025602:Halorhodopsins; C045073:Cre recombinase; D019426:Integrases