持续高频刺激改变短刺激产生的神经网络效应

Sustained High Frequency Stimulations Change The Effects on Neural Networks Induced by Short Stimulations

不同时长的电脉冲高频刺激(high frequency stimulation,HFS)对于脑神经系统具有不同的作用.其中,数秒时长的短促HFS可通过"点燃"效应制作动物癫痫模型,也可以产生长时间保持的突触可塑性变化,而数分钟以上的长时HFS却可以安全地用于临床的深部脑刺激,治疗多种脑疾病.因此推测,持续的HFS可以改变短促刺激产生的效应.为了验证此推测,在大鼠海马CA1区的输入轴突纤维Schaffer侧支上,分别施加5 s和2 min两种时长的100 Hz HFS,并监测刺激结束后下游神经元群体对于单脉冲测试的响应电位,即群峰电位(population spike,PS).结果显示,5 s短HFS结束时会紧跟后放电痫样活动,并且,从测试脉冲诱发的PS幅值和潜伏期可见,短HFS诱导的兴奋性增强可以维持数十分钟.反之,2 min的长HFS结束时紧随之后的是数十秒无发放活动的静息期,而且,PS在数分钟内即恢复到HFS前的基线水平.这些结果表明,长时HFS的后期刺激可以改变前期短促刺激对于下游神经网络的作用,即消除短刺激可能产生的长时程兴奋效应.此发现对于深入了解高频刺激的作用机制、促进深部脑刺激的临床应用具有重要意义.

High frequency stimulations（HFS） of electrical pulses with different durations have different effects on the nervous system in brain. A short HFS train with a duration of several seconds can be used to establish epilepsy models in animals via a ＂ kindling＂ effect. It can also produce changes of synaptic plasticity that may persist.However, a long HFS train with a duration several minutes or longer can be safely applied in deep brain stimulation to treat various brain diseases in clinic. Therefore, we speculate that a sustained HFS could change the neuronal responses induced by a short HFS. To verify this hypothesis, 100 Hz HFS with durations of 5 s and 2 min were applied to the Schaffer collateral of afferent fibers in the hippocampus CA1 region of rats. The response potentials of downstream populations of neurons, i.e., population spikes（PS）, evoked by a single test pulse were monitored after the termination of HFS trains. The evoked-PS potentials following the two types of stimulation were compared. The results showed that after-discharge events with epileptiform activity appeared immediately following 5 s short HFS trains. In addition, the changes of amplitude and latency of the evoked-PS suggest an increase of excitability persisting for tens of minutes after the termination of 5 s short HFS. In contrast, silent periods of a few tens of seconds without any neuronal firing appeared immediately following 2 min long HFS trains. Furthermore, the amplitude of evoked-PS by test pulses recovered to the baseline level in a few minutes after the termination of long HFS. Because long HFS trains include short HFS trains, these results indicate that the late stimulation of long trains can change the effects on the downstream neural networks produced by their early phases and eliminate the long-term excitatory effects induced by short trains. These findings are of significance for further revealing HFS mechanisms and for advancing the clinical applications of deep brain stimulation.