Abstracts

Rationale: Optogenetic tools comprise a variety of different light-sensitive proteins from single-cell organisms that can be expressed in mammalian neurons and effectively control their excitability. Expression of the inhibitory halorhodopsin (NpHR) in mammalian neurons make these optogenetic tools potent candidates in controlling hyperexcitatory neuronal firing in models of epilepsy.Our aim is to investigate the likelihood of the seizures arising within a more distributed limbic system and to identify the control area and neurons in the circuits involved in limbic epilepsy critical for both defining the focus for surgery and targeting pharmacotherapy to the right areas and cells.Methods: In this study, we examined the effect of silencing the functional activities of neurons either in CA1 region of the hippocampus or entorhinal cortex on the seizure onset triggered by acute amygdala electrical stimulation.Results: Our findings showed that there were transient and stable seizure onsets in this acute amygdala electrical stimulation model. Halorhodopsin activation in CA1 or entorhinal cortex by photostimulation suppressed or stopped the both the behavioral and electrographic seizures. Moreover, halorhodopsin activation enhanced the threshold for seizure onset.Conclusions: These results indicate that synchronous activity of large number of the principal cells either in the hippocampus or in the entorhinal cortex is crucial for generation of seizures and/or epileptogenesis in animal model of limbic epilepsy. Functional silencing of principal cells in the hippocampus or in the entorhinal cortex could be a potential therapy for limbic epilepsy.