Editors' ChoiceNeuroscience

Lights of Hope in the Treatment of Epilepsy

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Science Translational Medicine  13 Mar 2013:
Vol. 5, Issue 176, pp. 176ec44
DOI: 10.1126/scitranslmed.3006078

Of the 2 million people in the United States who suffer from epilepsy, nearly 40% still have seizures, even after medication or neurosurgery. Worse, these treatments are often associated with side effects that impair the patient’s daily life and long-term health. Better antiepileptic therapies are needed. Now, Paz and colleagues present intriguing data on the use of optogenetics to stop seizures in an animal model of epilepsy after stroke.

The authors created an ischemic stroke in the somatosensory cortex of rats with photothrombosis. About 1 week later, thalamocortical neurons began to exhibit spontaneous, rhythmic (epileptiform) discharges that were associated with a highly excitable network that had developed in the thalamus. Epileptic seizures commenced approximately 4 weeks after the stroke event.

The authors then used optogenetics in awake, freely moving rats to try to terminate the seizures by selectively inhibiting the thalamocortical neurons. To do so, they injected a viral vector that expressed a light-sensitive membrane ion channel [hyperpolarization-activated cyclic nucleotide–gated (HCN)] in the ventrobasal thalamus on the same side of the brain as the stroke. When illuminated, this protein reduces neuronal firing. An optic fiber implanted into the thalamus directed light from a laser to the channel-expressing neurons. The light treatment completely stopped the seizures, without affecting normal behavior.

The study has limitations in that the way the authors triggered the stroke in rats (photothrombosis) is different from the way stroke occurs in humans. And the viral construct and optogenetic approach have not been fully evaluated for human use. Nevertheless, these results raise the possibility that optogenetics may be used in the future as a highly effective and targeted therapy for epilepsy.

J. T. Paz et al., Closed-loop optogenetic control of thalamus as a tool for interrupting seizures after cortical injury. Nat Neurosci. 16, 64–70 (2013). [Full text]

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