title: Optical control of focal epilepsy in vivo with caged γ-aminobutyric acid.
abstract: OBJECTIVE
  There is enormous clinical potential in exploiting the spatial and temporal resolution of optical techniques to modulate pathophysiological neuronal activity, especially intractable focal epilepsy. We have recently utilized a new ruthenium-based caged compound, ruthenium-bipyridine-triphenylphosphine-γ-aminobutyric acid (RuBi-GABA), which releases GABA when exposed to blue light, to rapidly terminate paroxysmal activity in vitro and in vivo.
  
  
  METHODS
  The convulsant 4-aminopyridine was used to induce interictal activity and seizures in rat neocortical slices and anesthetized rats. We examined the effect of blue light, generated by a small, light-emitting diode (LED), on the frequency and duration of ictal activity in the presence and absence of RuBi-GABA.
  
  
  RESULTS
  Neither blue light alone, nor low concentrations of RuBi-GABA, affected interictal activity or baseline electrical activity in neocortical slices. However, brief, blue illumination of RuBi-GABA, using our LED, dramatically reduced extracellular spikes and bursts. More impressively, illumination of locally applied RuBi-GABA rapidly terminated in vivo seizures induced by topical application of 4-aminopyridine. The RuBi-GABA effect was blocked by the GABA(A) antagonist picrotoxin, but not duplicated by direct application of GABA.
  
  
  CONCLUSIONS
  This is the first example of optical control of in vivo epilepsy, proving that there is sufficient cortical light penetration from an LED and diffusion of caged GABA to quickly terminate intense focal seizures. We are aware that many obstacles need to be overcome before this technique can be translated to patients, but at the moment, this represents a feasible method for harnessing optical techniques to fabricate an implantable device for the therapy of neocortical epilepsy.
authors.affiliation: Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55355, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Rode
authors.forename: Darcy S
authors.initials: DS
authors.lastname: Peterka
authors.forename: Rafael
authors.initials: R
authors.lastname: Yuste
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rothman
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage*; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012428:Ruthenium / Q000008:administration & dosage*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D005680:gamma-Aminobutyric Acid; D012428:Ruthenium