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Objective: The subiculum, one major output structure in the hippocampus, is considered to participate in seizure generation and modulation in temporal lobe epilepsy (TLE) since stimulation of the subiculum was found to suppress seizures in a seizure model. The current study aimed to investigate whether acute scheduled or responsive stimulation of the subiculum can suppress spontaneous seizures and affect local excitability of the subiculum in a chronic TLE model. Methods: Wistar rats were administrated intraperitoneally with kainic acid (KA) repeatedly to induce status epilepticus (SE). 4 months later the rats were implanted with stimulation electrodes in the subiculum. After one-week baseline recording, they received either responsive or scheduled high frequency stimulation (HFS, 125 Hz) for two days and then were swapped to the other type of stimulation for two days with one-week interval. All the rats also received pulse stimuli (100 μs, interval of 5-7 s) at different intensities (20, 50, 100 mA) before and after stimulation while evoked responses were elicited. Results: Acute HFS of the subiculum-both scheduled and responsive stimulation-suppressed spontaneous focal seizures in rats. The excitability of the subiculum, measured by evoked responses, did not show obvious changes before and after HFS. Conclusion: The preliminary outcomes revealed the anticonvulsant effects of subicular stimulation on spontaneous seizures, suggesting that the subiculum is a promising target candidate for deep brain stimulation to control seizures in TLE. The absence of changes in subicular excitability indicates that HFS affects the hippocampal network rather than the excitability of the subiculum per se.

Effects of Responsive and Scheduled Stimulation in the Subiculum on Seizures and Excitability in the Kainate Induced Temporal Lobe Epilepsy Model