title: Optical triggered seizures using a caged 4-Aminopyridine.
abstract: Animal models of epilepsy are critical not only for understanding the fundamental mechanism of epilepsy but also for testing the efficacy of new antiepileptic drugs and novel therapeutic interventions. Photorelease of caged molecules is widely used in biological research to control pharmacologic events with high spatio-temporal resolution. We developed a technique for in vivo optical triggering of neocortical seizures using a novel caged compound based on ruthenium photochemistry (RuBi-4AP). Epileptiform events in mouse cortex were induced with blue light in both whole brain and focal illumination. Multi-electrode array recording and optical techniques were used to characterize the propagation of these epileptic events, including interictal spikes, polyspikes, and ictal discharges. These results demonstrate a novel optically-triggered seizure model, with high spatio-temporal control, that could have widespread application in the investigation of ictal onset, propagation and to develop novel light-based therapeutic interventions.
authors.affiliation: Department of Neurological Surgery, Brain and Mind Center, New York Presbyterian Hospital, Weill Medical College of Cornell University New York, NY, USA.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Biological Sciences, Columbia University New York, NY, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: McGarry
authors.affiliation: Department of Neurological Surgery, Brain and Mind Center, New York Presbyterian Hospital, Weill Medical College of Cornell University New York, NY, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Neurological Surgery, Brain and Mind Center, New York Presbyterian Hospital, Weill Medical College of Cornell University New York, NY, USA ; Department of Psychology, University of Sheffield Sheffield, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Harris
authors.affiliation: Department of Psychology, University of Sheffield Sheffield, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Berwick
authors.affiliation: Department of Biological Sciences, Columbia University New York, NY, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Yuste
authors.affiliation: Department of Neurological Surgery, Brain and Mind Center, New York Presbyterian Hospital, Weill Medical College of Cornell University New York, NY, USA.
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Schwartz
keywords: caged compound; electrophysiology; epilepsy model; neocortex; optical imaging; photostimulation