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.