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.
Highlights
Epilepsy is a disease that affects about 1% of the population in the United States involving recurrent seizures, or ictal events (Thurman et al, 2011)
2 μl RuBi-4-AP solution was injected in neocortex at the depth of 300 μm using an UltraMicroPump (UMP-3, WPI, Sarasota, FL) via a glass electrode controlled at a speed of 100 nl/min
Once the surgery was complete, we recorded baseline local field potential (LFP) signals for 15 min to ensure the health of the neocortex and the absence of any abnormal activity that might result from the trauma of surgery
Summary
Epilepsy is a disease that affects about 1% of the population in the United States involving recurrent seizures, or ictal events (Thurman et al, 2011). The lifelong effects of chronic epilepsy can be devastating due to progressive cognitive decline from short duration electrical discharges that occur throughout the epileptic network between seizures called interictal events. The mechanism of neocortical epilepsy is poorly understood (Navarro et al, 2002). Animal models of epilepsy are very important for understanding the fundamental mechanisms of epilepsy and for testing the efficacy of new antiepileptic drugs or other therapeutic interventions (Löscher, 2011). Called phototriggers, are widely used in biological research. The ability of such caged compounds to trigger seizures and interictal events has not been previously investigated
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