生物医学工程学杂志

生物医学工程学杂志

高频电刺激改变神经元发放与场电位节律之间的锁相关系

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临床上,已将深部脑刺激(DBS)技术成功应用于治疗多种脑部疾病。近年的研究推测,DBS 技术使用的电脉冲高频刺激(HFS)可以改变神经元动作电位的病理性节律发放,这可能是 DBS 治疗脑部疾病的重要机制之一,但是这种推测尚需实验数据的证实。本文在已麻醉的大鼠海马 CA1 区的输入轴突束薛氏侧支(Schaffer collaterals)施加时长为 1 min、频率为 100 Hz 的 HFS,并分析刺激下游 CA1 区的锥体神经元和中间神经元的锋电位,考察两种神经元的节律性动作电位发放的变化情况。结果显示,麻醉大鼠 CA1 区的场电位存在明显的 θ 节律,且在顶树突层尤其明显,而神经元锋电位与 θ 节律存在锁相关系。与此基线记录相比较,在 HFS 期间,锥体神经元的锋电位与顶树突层 θ 节律的锁相值从 0.36 ± 0.12 显著减小至 0.06 ± 0.04(P < 0.001,配对 t 检验,N = 8);中间神经元锋电位的锁相值也从 0.27 ± 0.08 减小至 0.09 ± 0.05(P < 0.01,配对 t 检验,N = 8)。两类神经元与胞体层 θ 节律的锁相关系也有类似改变。此结果表明,对轴突束施加 HFS 可以消除下游神经元动作电位发放与场电位 θ 节律之间的锁相关系,改变神经元的节律性发放模式。这种现象产生的机制可能是 HFS 诱导的轴突传导障碍,此发现对于深入研究 DBS 的作用机制具有重要的意义。

Deep brain stimulation (DBS) has been successfully used to treat a variety of brain diseases in clinic. Recent investigations have suggested that high frequency stimulation (HFS) of electrical pulses used by DBS might change pathological rhythms in action potential firing of neurons, which may be one of the important mechanisms of DBS therapy. However, experimental data are required to confirm the hypothesis. In the present study, 1 min of 100 Hz HFS was applied to the Schaffer collaterals of hippocampal CA1 region in anaesthetized rats. The changes of the rhythmic firing of action potentials from pyramidal cells and interneurons were investigated in the downstream CA1 region. The results showed that obvious θ rhythms were present in the field potential of CA1 region of the anesthetized rats. The θ rhythms were especially pronounced in the stratum radiatum. In addition, there was a phase-locking relationship between neuronal spikes and the θ rhythms. However, HFS trains significantly decreased the phase-locking values between the spikes of pyramidal cells and the θ rhythms in stratum radiatum from 0.36 ± 0.12 to 0.06 ± 0.04 (P < 0.001, paired t-test, N = 8). The phase-locking values of interneuron spikes were also decreased significantly from 0.27 ± 0.08 to 0.09 ± 0.05 (P < 0.01, paired t-test, N = 8). Similar changes were obtained in the phase-locking values between neuronal spikes and the θ rhythms in the pyramidal layer. These results suggested that axonal HFS could eliminate the phase-locking relationship between action potentials of neurons and θ rhythms thereby changing the rhythmic firing of downstream neurons. HFS induced conduction block in the axons might be one of the underlying mechanisms. The finding is important for further understanding the mechanisms of DBS.

关键词: 高频电刺激; 锋电位; 节律性发放; θ 节律; 锁相

Key words: high frequency stimulation; spike; rhythmic firing; θ rhythm; phase-locking

引用本文: 马维健, 封洲燕, 周文杰, 王兆祥, 蔡紫燕. 高频电刺激改变神经元发放与场电位节律之间的锁相关系. 生物医学工程学杂志, 2018, 35(1): 1-7. doi: 10.7507/1001-5515.201706073 复制

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