Investigation Of The Effects On Neuronal Activity Of Hippocampal CA1 Region By Electrical Pulse Stimulations With Different Frequencies

Deep brain stimulation(DBS),as a new alternative method to drugs and traditional lesion surgery,has shown good application prospects in the treatment of neurological diseases such as epilepsy.However,the influence of different stimulation parameters on the effect of DBS and its mechanism have not been clearly determined.The stimulation frequency is one of the main parameters of DBS.The effect of stimulation with different frequencies on neuronal activity has always been one of the focuses of DBS research.It is still impossible to determine for which frequency of electrical stimulation can better inhibit the onset of epilepsy.Therefore,studying the effects of pulse stimulation with different frequencies on neuronal activity is of great significance for advancing the application of DBS in the clinical treatment of epilepsy.In this study,rat hippocampus was used as the research object.The electric pulse stimulation with different frequencies(10-400 Hz)was applied to the Schaffer collateral branch of CA1 area.The duration of stimulation was divided into long term(1 min)and short term(0.5 s)to investigate the activities of downstream intemeurons and pyramidal cells,and to analyze the possible mechanisms.The main findings are as follows:(1)Long-term and low-frequency stimulation can inhibit the activity of pyramidal cellsWhen 1 min long-term stimulation with frequency of 10 and 20 Hz was applied to the Schaffer collateral,the action potentials(ie,spike)of main neurons(pyramidal cells)in the hippocampal CA1 region were significantly reduced during stimulation.And there was a suppression period of the spike potential of about 15-30 ms in the peri-stimulus time histogram and inter-spike-interval.Meanwhile,the time correlation between the spike and the stimulation pulse was weak,indicating that the main neurons are not directly regulated by stimulation.At this time,the firing rate of intemeurons did not change significantly,but the time correlation between the spikes and the stimulation pulse was strong,and the latency and its variation were small,indicating that the intemeurons were directly stimulated and regulated by pulses.Pulse stimulation may inhibit pyramidal cells’ activities by activating the intemeurons with lower threshold and their inhibitory synapses.(2)Long-term and high-frequency stimulation can enhance the activity of pyramidal cellsDuring high-frequency stimulation(50 and 100 Hz),for pyramidal cells,the proportion of spikes concentrated in the Inter-spike.interval increased.However,for intemeurons,the mean firing rate decreased.It was shown that the excitation to interneurons from electrical stimulations with low frequency and high frequency were similar,but high-frequency stimulation may cause the interneurons to be non-synchronized during stimulation through axonal conduction block,which leads to the inhibition of pyramidal neurons.(3)Short-term and low-frequency stimulation can inhibit the activity of pyramidal cells,while high-frequency stimulation can excite the activity of interneurons and pyramidal cellsDuring the short-term stimulation(10 and 20 Hz),the firing rate of pyramidal cells significantly reduced.The possible mechanism may be that the stimulation activated the inhibitory synapses associated with the interneurons,thereby inhibiting the activity of pyranidal cells.When the stimulation frequency was higher than 100 Hz,the firing rate of two types of neurons during stimulation would increase significantly.It was probably because that the excitation from stimulation to neurons stimulateso vercame the inhibition of interneurons,thus the net excitatory effect increased the firing of neurons.In summary,by examining the effects of pulse stimulation with different frequencies and different durations on downstream intemeurons and pyramidal cells,we discovered that long-term and short-term stimulation can effectively with low-frequency can inhibit the activity of primary neurons;short-term stimulation with high-frequency could obviously excite the activity of two types of neurons since it could not induce axonal conduction block like long-term stimulation with high-frequency.These results can provide guidance about stimulation parameter for DBS treatment in epilepsy using open-loop stimulation and adjustable closed-loop stimulation,which is of great significance for the clinical application of DBS.