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Published 2013 | Published + Supplemental Material
Journal Article Open

Optogenetic Delay of Status Epilepticus Onset in an In Vivo Rodent Epilepsy Model


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.

Additional Information

© 2013 Sukhotinsky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received November 14, 2012; Accepted March 16, 2013; Published April 24, 2013. We thank Drs. Andrew Cole, Matt Bianchi, and members of Dr. Cash's laboratory for their insightful comments on the manuscript, especially Justine Cormier. Funding: DOD grant # W81xWH-09-1-0480. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Supplemental Material - journal.pone.0062013.s002.docx


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August 19, 2023
October 20, 2023