Suppressing synchronous firing of epileptiform activity by high-frequency stimulation of afferent fibers in rat hippocampus

Abstract

Aims: Deep brain stimulation (DBS) is a promising technology for treating epilepsy. However, the efficacy and underlying mechanisms of the high-frequency stimulation (HFS) utilized by DBS to suppress epilepsy remain uncertain. Previous studies have shown that HFS can desynchronize the firing of neurons. In this study, we investigated whether the desynchronization effects of HFS can suppress epileptiform events. Methods: HFS trains with seconds of duration (short) and a minute of duration (long) were applied at the afferent fibers (ie, Schaffer collaterals) of the hippocampal CA1 region in anesthetized rats in vivo. The amplitude and the rate of population spikes (PS) appeared in the downstream of stimulation were calculated to evaluate the intensity of synchronized firing of neuronal populations between short and long HFS groups. A test of paired-pulse depression (PPD) was used to assess the alteration of inhibitory neuronal circuits. Results: The sustained stimulation of a 60-s long HFS suppressed the afterdischarges that were induced by a 5-s short HFS to impair the local inhibitions. During the sustained HFS, the mean PS amplitude reduced significantly and the burst firing decreased, while the amount of neuronal firing did not change significantly. The paired-pulse tests showed that with a similar baseline level of small PS2/PS1 ratio indicating a strong PPD, the 5-s HFS increased the PS2/PS1 ratio to a value that was significantly greater than the corresponding ratio during sustained HFS, indicating that the PPD impaired by a short HFS may be restored by a sustained HFS. Conclusions: The sustained HFS can desynchronize the population firing of epileptiform activity and accelerate a recovery of inhibitions to create a balance between the excitation and the inhibition of local neuronal circuits. The study provides new clues for further understanding the mechanism of DBS and for advancing the clinical application of DBS in treating epilepsy.