title: Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.
abstract: Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy.
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007.
authors.forename: Colin
authors.initials: C
authors.lastname: Soper
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007.
authors.forename: Evan
authors.initials: E
authors.lastname: Wicker
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007.
authors.forename: Catherine V
authors.initials: CV
authors.lastname: Kulick
authors.affiliation: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007; Department of Pediatrics, Georgetown University, Washington, DC 20007.
authors.forename: Prosper
authors.initials: P
authors.lastname: N'Gouemo
authors.affiliation: Department of Pharmacology & Physiology, Georgetown University, Washington, DC 20007; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007. Electronic address: Paf22@georgetown.edu.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Forcelli
mesh_terms: D015107:4-Butyrolactone; D000161:Acoustic Stimulation; D000818:Animals; D001933:Brain Stem / Q000503:physiopathology; D004195:Disease Models, Animal; D000069280:Electrocorticography; D004827:Epilepsy / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D010433:Pentylenetetrazole; D016548:Prosencephalon / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013477:Superior Colliculi / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology
chemical_list: D015107:4-Butyrolactone; D010433:Pentylenetetrazole
keywords: Absence epilepsy; Channelrhodopsin-2; Deep brain stimulation; Generalized epilepsy; Partial seizure; Rat; Temporal lobe epilepsy