Unlike electrical stimulation, optogenetics allows neuronal manipulation with great cell-type specificity, with light directly affecting only those cells expressing opsins. In a recent report in Nature Communications, Krook-Magnuson et al harnessed this specificity to stop seizures in vivo in a mouse model of temporal lobe epilepsy. Mice were implanted with electrodes to record brain activity and 200µm thick optical fibers to deliver light to the brain. A closed-loop, on-demand responsive system detected seizures in real time, allowing temporal specificity, in addition to the cell-type specificity achieved through selective opsin expression. Specifically, the authors either selectively inhibited excitatory principal cells or, alternatively, excited a subpopulation of GABAergic inhibitory neurons in the hippocampus by delivering light at the time of a seizure. Both approaches proved successful, despite the less than 5% of illuminated neurons expressing opsins in the latter approach. Light arrested ongoing electrical seizure activity and reduced the incidence of events progressing to overt behavioral seizures.
Epilepsy, a condition of recurrent, spontaneous seizures, is a prevalent disorder, with 1 out of 26 people developing epilepsy during their lifetime. Unfortunately, for over 40% of patients, seizures cannot be controlled with current treatment options. Temporal lobe epilepsy, the most common form of epilepsy in adults, is often pharmacoresistant, and current systemic treatments have major side-effects. By demonstrating the successful use of optogenetics in a mouse model of temporal lobe epilepsy, Krook-Magnuson et al highlight the potential of an intervention for this devastating disease which would directly affect only a minimum number of cells, and only at the time of seizures.
Previous work in other laboratories further supports the use of these techniques in the treatment of epilepsy. Responsive electrical stimulation devices for the treatment of epilepsy are in clinical trials (Morrell 2011), and recent reports have used optogenetics to stop seizure activity both in vitro (Tonnesen et al 2009) as well as in other models of epilepsy in vivo (Wykes et al, 2012; Paz et al, 2013). Taken together, these findings suggest that we may one day be able to use optogenetic stop lights for the treatment of epilepsy.