Journal
NEUROBIOLOGY OF DISEASE
Volume 87, Issue -, Pages 102-115Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2015.12.012
Keywords
Absence epilepsy; Temporal lobe epilepsy; Generalized epilepsy; Rat; Channelrhodopsin-2; Partial seizure; Deep brain stimulation
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Funding
- Georgetown-Howard Universities Center for Clinical and Translational Science [UL1TR000101, UL1TR001409]
- Georgetown University Medical Center Dean for Research
- American Epilepsy Society/Epilepsy Foundation of America
- National Institutes of Health [HD046388, KL2TR001432, AA020073]
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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 (DISC) to fill this role. Optogenetic activation of DISC 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 DISC, and not neighboring structures. DISC 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 DISC is a promising target for optogenetic control of epilepsy. (C) 2015 Elsevier Inc. All rights reserved.
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