title: Optogenetic approaches to treat epilepsy.
abstract: BACKGROUND
  Novel treatments for drug-resistant epilepsy are required.
  
  
  METHODS
  Optogenetics is a combination of optical and genetic methods used to control the activity of specific populations of excitable cells using light with high temporal and spatial resolution. Derived from microbial organisms, 'opsin' genes encode light-activated ion channels and pumps. Opsins can be genetically targeted to well-defined neuronal populations in mammalian brains using viral vectors. When exposed to light of an appropriate wavelength, the excitability of neurons can be increased or decreased optically on a millisecond timescale.
  
  
  CONCLUSIONS
  Alternative treatments for drug-resistant epilepsy such as vagal, cortical or subcortical stimulation, focal cooling, callosotomy, or ketogenic diet have met with limited success, whereas optogenetic approaches have shown considerable pre-clinical promise.
  
  
  CONCLUSIONS
  Several groups have reported that optogenetic approaches successfully attenuated epileptiform activity in different rodent models of epilepsy, providing proof of the principle that this approach may translate to an effective treatment for epilepsy patients. However, further studies are required to determine the optimal opsin, in which types (or subtypes) of neurons it should be expressed, and what are the most efficient temporal profiles of photostimulation. Although invasive due to the need to inject a viral vector into the brain and implant a device to deliver light to opsin-transduced neurons, this approach has the potential to be effective in suppressing spontaneous seizures while avoiding the side-effects of anti-epileptic drugs (AEDs) or the need to permanently excise regions of the brain. Optogenetic approaches may treat drug-refractory epilepsies.
authors.affiliation: Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, University College London, UK. Electronic address: r.wykes@ucl.ac.uk.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wykes
authors.affiliation: Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, University College London, UK.
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.affiliation: Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, University College London, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavlov
authors.affiliation: Department of Clinical & Experimental Epilepsy, UCL Institute of Neurology, University College London, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magloire
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055355:Opsins / Q000235:genetics / Q000378:metabolism*; D062308:Optogenetics / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D009419:Nerve Tissue Proteins; D055355:Opsins
keywords: Epilepsy; Gene therapy; Optogenetics