Abstracts

Rationale: Epilepsy is a clinical term referring to a disease that affects between 1 and 2% of the population. The mechanism of neocortical epilepsy is poorly understood. Animal models of epilepsy are very important not only for understanding the fundamental mechanism of epilepsy but also for testing the efficacy of new antiepileptic drugs or other therapeutic interventions. New neuroimaging and neuro-modulatory techniques such as optogenetics have emerged as a popular tool to probe and control neuronal function with light. Caged compounds, also called phototriggers, are widely used in biological research. Photorelease of caged molecules can control neurophysiology with high spatial-temporal resolution. However, the efficacy of such caged compounds to model epilepsy remains unknown. Methods: Ruthenium-bipyridine-triphenylphosphine caged 4-aminopyridine (Rubi-4AP) was topically applied on the mouse neocortex. The light source for uncaging was a 470 nm LED light (Thorlabs, Newton, NJ). The local field potential was recorded to identify the ictal and interictal discharges. Results: 4-Aminopyridine (4-AP) is a potent convulsant when applied to the neocortex. Rubi-4AP is very stable in the solution. Baseline LFP recording showed normal brain activity both before Rubi-AP application with blue light illumination and after Rubi-4AP application before uncaging. Epileptiform events including interictal spikes, polyspikes, and ictal discharges were induced by blue visual light illumination (N= 5 mouse). Conclusions: These results demonstrated that we have developed a new acute experimental epilepsy model induced by a light. The next step is to optically manipulate epilepsy in multiple focal locations, alongside other optical methods for monitoring seizure spread.