Mode-dependent effect of low-frequency stimulation targeting the hippocampal CA3 subfield on amygdala-kindled seizures in rats

Brain stimulation with low-frequency stimulation (LFS) is emerging as an alternative treatment for refractory epilepsy. The present study aimed to investigate the effects of LFS targeting the hippocampal CA3 subfield in different modes on amygdala-kindled seizures in Sprague-Dawley rats. When fully kindled seizures were achieved by daily electrical stimulation of the amygdala, LFS (15 min train of 0.1 ms pulses at 1 Hz and 100 μA) of the CA3 was applied in several modes. Post-treatment with LFS significantly reduced the severity of and susceptibility to evoked seizures, whereas pre-treatment with LFS resulted in a similar but much weaker inhibition of seizures. Interestingly, prior consecutive daily application of LFS in the absence of kindling stimulation did not reduce subsequent evoked seizures, but abolished the anti-epileptic effect of post-treatment. These results indicated that LFS of the CA3 is able to reduce kindled seizures in a mode-dependent manner without cumulative feature. The hippocampal CA3 subfield could be considered as a potential target for epilepsy treatment using LFS, and should be delivered in an appropriate stimulation mode.