On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy

Nat Commun. 2013:4:1376. doi: 10.1038/ncomms2376.

Abstract

Temporal lobe epilepsy is the most common type of epilepsy in adults, is often medically refractory, and due to broad actions and long-time scales, current systemic treatments have major negative side-effects. However, temporal lobe seizures tend to arise from discrete regions before overt clinical behaviour, making temporally and spatially specific treatment theoretically possible. Here we report the arrest of spontaneous seizures using a real-time, closed-loop, response system and in vivo optogenetics in a mouse model of temporal lobe epilepsy. Either optogenetic inhibition of excitatory principal cells, or activation of a subpopulation of GABAergic cells representing <5% of hippocampal neurons, stops seizures rapidly upon light application. These results demonstrate that spontaneous temporal lobe seizures can be detected and terminated by modulating specific cell populations in a spatially restricted manner. A clinical approach built on these principles may overcome many of the side-effects of currently available treatment options.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Channelrhodopsins
  • Computer Systems
  • Disease Models, Animal
  • Electroencephalography
  • Epilepsy, Temporal Lobe / diagnosis*
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / pathology
  • Epilepsy, Temporal Lobe / physiopathology
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / pathology
  • GABAergic Neurons / radiation effects
  • Halorhodopsins / metabolism
  • Hippocampus / physiopathology
  • Integrases / metabolism
  • Light
  • Mice
  • Optogenetics / methods*
  • Seizures / diagnosis*
  • Seizures / genetics
  • Seizures / pathology
  • Seizures / physiopathology

Substances

  • Channelrhodopsins
  • Halorhodopsins
  • Cre recombinase
  • Integrases