Jensen A L, Durand D M
Neural Engineering Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
J Neural Eng. 2007 Jun;4(2):1-16. doi: 10.1088/1741-2560/4/2/001. Epub 2007 Jan 24.
Deep brain stimulation (DBS), also known as high frequency stimulation (HFS), is a well-established therapy for Parkinson's disease and essential tremor, and shows promise for the therapeutic control of epilepsy. However, the direct effect of DBS on neural elements close to the stimulating electrode remains an important unanswered question. Computational studies have suggested that HFS has a dual effect on neural elements inhibiting cell bodies, while exciting axons. Prior experiments have shown that sinusoidal HFS (50 Hz) can suppress synaptic and non-synaptic cellular activity in several in vitro epilepsy models, in all layers of the hippocampus. However, the effects of HFS on axons near the electrode are still unclear. In the present study, we tested the hypothesis that HFS suppresses axonal conduction in vitro. Sinusoidal HFS was applied to the alvear axon field of transverse rat hippocampal slices. The results show that HFS suppresses the alvear compound action potential (CAP) as well as the CA1 antidromic evoked potential (AEP). Complete suppression was observed as a 100% reduction in the amplitude of the evoked field potential for the duration of the stimulus. Evoked potential width and latency were not significantly affected by sinusoidal HFS. Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic transmission. The frequency dependence of sinusoidal HFS is similar to that observed in clinical DBS, with maximal suppression between 50 and 200 Hz. HFS produced not only suppression of axonal conduction but also a correlated rise in extracellular potassium. These data provide new insights into the effects of HFS on neuronal elements, and show that HFS can block axonal activity through non-synaptic mechanisms.
深部脑刺激（DBS），也称为高频刺激（HFS），是一种已被广泛应用于治疗帕金森病和特发性震颤的疗法，并且在癫痫的治疗控制方面也显示出前景。然而，DBS对刺激电极附近神经元件的直接影响仍然是一个重要的未解决问题。计算研究表明，HFS对神经元件具有双重作用，抑制细胞体，同时兴奋轴突。先前的实验表明，正弦HFS（50Hz）可以在几种体外癫痫模型中抑制海马各层的突触和非突触细胞活动。然而，HFS对电极附近轴突的影响仍不清楚。在本研究中，我们测试了HFS在体外抑制轴突传导的假设。将正弦HFS应用于大鼠横向海马切片的齿状回轴突场。结果表明，HFS抑制齿状回复合动作电位（CAP）以及CA1逆向诱发电位（AEP）。在刺激持续时间内，观察到诱发电场电位幅度降低100%，即完全抑制。诱发电位宽度和潜伏期不受正弦HFS的显著影响。抑制作用取决于HFS的幅度和频率，但与刺激持续时间和突触传递无关。正弦HFS的频率依赖性与临床DBS中观察到的相似，在50至200Hz之间抑制作用最大。HFS不仅抑制轴突传导，还导致细胞外钾离子相关升高。这些数据为HFS对神经元元件的影响提供了新的见解，并表明HFS可以通过非突触机制阻断轴突活动。
