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.

Electrical stimulation in the brain is an emerging therapy for treating a wide range of neurological disorders. Although electrical pulses are commonly used in the clinic, other electrical waveforms such as sinusoidal-waves have been investigated to improve the therapeutic efficacy, to reduce the risk of tissue damage induced by stimulation, and to decrease the consumption of electrical energy. However, the effects of sinusoidal stimulation on neuronal activity are still unclear. In the present study, we investigated the neuronal responses to the stimulation of 50-Hz sinusoidal-waves applied on the afferent fibers of the neurons in the hippocampal CA1 region of Sprague-Dawley rat in vivo. Results show that the stimulation increased the firing rate of both pyramidal neurons and interneurons in the downstream region of stimulation. Also, the stimulation eliminated the original theta rhythms (2-5 Hz) in the singleunit activity of the two types of neurons and entrained these neurons to fire at the stimulation rhythm. These results provide new clues for the mechanisms of brain stimulation to suppress the pathological rhythms in the neuronal activity, and for the application of sinusoidal waveforms in brain stimulation therapy.

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