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Beyond the hammer and the scalpel: selective circuit control for the epilepsies

Abstract

Current treatment options for epilepsy are inadequate, as too many patients suffer from uncontrolled seizures and from negative side effects of treatment. In addition to these clinical challenges, our scientific understanding of epilepsy is incomplete. Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. Such specificity of intervention also has the potential for direct therapeutic benefits, allowing healthy tissue and network functions to continue unaffected. In this Perspective, we discuss promising uses of these technologies for the study of seizures and epilepsy, as well as potential use of these strategies for clinical therapies.

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Figure 1: DREADD-mediated attenuation of acute seizures.
Figure 2: On-demand inhibition of spontaneous seizures.

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Acknowledgements

This work was funded by US National Institutes of Health grants NS35915 and NS74702 (to I.S.), a Citizens United for Research in Epilepsy (CURE) Taking Flight Award (to E.K.-M.), and a US National Institutes of Health grant K99NS087110 (to E.K.-M.).

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Correspondence to Esther Krook-Magnuson or Ivan Soltesz.

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Krook-Magnuson, E., Soltesz, I. Beyond the hammer and the scalpel: selective circuit control for the epilepsies. Nat Neurosci 18, 331–338 (2015). https://doi.org/10.1038/nn.3943

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