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 revealed that GABAergic 
neurotransmission activated by optical stimulation was responsible for the 
suppression.