Sinusoidal stimulation trains suppress epileptiform spikes induced by 4-AP in the rat hippocampal CA1 region in-vivo

Abstract

Deep brain stimulation (DBS) shows promises in the treatment of refractory epilepsy. Due to the complex causes of epilepsy, the mechanisms of DBS are still unclear. Depolarization block caused by the persistent excitation of neurons may be one of the possible mechanisms. To test the hypothesis, 4-aminopyridine (4-AP) was injected in rat hippocampal CA1 region in-vivo to induce epileptiform activity. Sinusoidal stimulation trains were applied to the afferent pathway (Schaffer collaterals) of CA1 region to suppress the epileptiform spikes. Results show that 2-min long trains of sinusoidal stimulation (50 Hz) decreased the firing rate of population spikes (PS) and decreased the PS amplitudes significantly. In addition, small positive sharp waves replaced PS activity during the periods of stimulation. A lower frequency sinusoidal stimulation (10 Hz) failed to decrease the firing rate of PS, but decreased the PS amplitudes significantly. These results suggest that stimulation trains of sinusoidal waves could suppress epileptiform spikes. Presumably, the stimulation with a high enough frequency might excite the downstream neurons persistently and elevate the membrane potentials continuously, thereby cause depolarization blocks in the neurons. The findings of the study provide insights in revealing the mechanisms of DBS, and have important implications to the clinical treatment of epilepsy.

Sinusoidal stimulation on afferent fibers modulates the firing pattern of downstream neurons in rat hippocampus

“…Previous studies of animal experiments and computational simulations have shown the effects of sinusoidal stimulations on abnormal neuronal activity in the brain. For example, experimental studies have shown that sinusoidal stimulations may suppress epileptiform activity in the hippocampal CA1 region (Bikson et al, 2001;Guo et al, 2016;Lian et al, 2003). Simulation studies have shown that sinusoidal stimulations with low current intensity can alleviate the spontaneous oscillations in the pathological globus pallidus and subthalamic nucleus network in Parkinson's state (Liu et al, 2018).…”