title: Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.
abstract: Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.
authors: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Inna
authors: I
authors: Sukhotinsky
authors: Alexander M
authors: AM
authors: Chan
authors: Omar J
authors: OJ
authors: Ahmed
authors: Vikram R
authors: VR
authors: Rao
authors: Viviana
authors: V
authors: Gradinaru
authors: Charu
authors: C
authors: Ramakrishnan
authors: Karl
authors: K
authors: Deisseroth
authors: Ania K
authors: AK
authors: Majewska
authors: Sydney S
authors: SS
authors: Cash
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D015870:Gene Expression; D025602:Halorhodopsins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D062308:Optogenetics / Q000009:adverse effects / Q000379:methods*; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D013226:Status Epilepticus / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D014161:Transduction, Genetic
chemical_list: D025602:Halorhodopsins
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