Highlights
- •High frequency optogenetic stimulation induces acute seizure suppression.
- •Optical stimulation suppresses focal and distal epileptiform activity.
- •Seizure suppression decreases over time but can be reinstated by intermittent stimulation.
- •GABA transmission activated by optical stimulation is implicated in seizure suppression.
Abstract
Background
Electrical high frequency stimulation (HFS) has been shown to suppress seizures. However,
the mechanisms of seizure suppression remain unclear and techniques for blocking specific
neuronal populations are required.
Objective
The goal is to study the optical HFS protocol on seizures as well as the underlying
mechanisms relevant to the HFS-mediated seizure suppression by using optogenetic methodology.
Methods
Thy1-ChR2 transgenic mice were used in both vivo and in vitro experiments. Optical stimulation with pulse trains at 20 and 50 Hz was applied on
the focus to determine its effects on in vivo seizure activity induced by 4-AP and recorded in the bilateral and ipsilateral-temporal
hippocampal CA3 regions. In vitro methodology was then used to study the mechanisms of the in vivo suppression.
Results
Optical HFS was able to generate 82.4% seizure suppression at 50 Hz with light power
of 6.1 mW and 80.2% seizure suppression at 20 Hz with light power of 2.0 mW. The suppression
percentage increased by increasing the light power and saturated when the power reached
above-mentioned values. In vitro experimental results indicate that seizure suppression was mediated by activation
of GABA receptors. Seizure suppression effect decreased with continued application
but the suppression effect could be restored by intermittent stimulation.
Conclusions
This study shows that optical stimulation at high frequency targeting an excitatory
opsin has potential therapeutic application for fast control of an epileptic focus.
Furthermore, electrophysiological observations of extracellular and intracellular
signals reveled that GABAergic neurotransmission activated by optical stimulation
was responsible for the suppression.
Keywords
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Article info
Publication history
Published online: July 18, 2014
Accepted:
July 13,
2014
Received in revised form:
June 17,
2014
Received:
March 18,
2014
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
