深部脑刺激期间神经元锋电位波形变化及其机制研究

发布时间：2018-06-02 03:06

本文选题：高频电刺激(HFS) + 海马CA1区　；参考：《浙江大学》2017年硕士论文

【摘要】：深部脑刺激(deep brain stimulation,DBS)是神经工程领域的研究热点之一。临床上,利用DBS中的高频电刺激(high frequency stimulation,HFS)治疗帕金森氏症、癫痫等脑神经系统疾病已经取得了令人瞩目的疗效,但其作用机制依然存在争议。研究电刺激期间神经元活动的变化是揭示DBS机制的重要方法,而利用微电极阵列技术可以在细胞外同时记录多个神经元的动作电位(即锋电位)信号,为DBS的深入研究提供重要信息。但是,HFS期间锋电位波形会产生变化,这一方面给锋电位的检测和跟踪造成了困难,另一方面也可能为研究DBS提供线索。因此,本文通过麻醉大鼠的在体实验,在海马CA1区输入及输出轴突上施加1～2 min时长的100 Hz或200 Hz顺向高频电刺激(orthodromic-HFS,O-HFS)和逆向高频电刺激(antidromic-HFS,A-HFS),研究正确跟踪神经元单元锋电位的方法,分析锋电位波形特征参数的变化及其可能机制。此外,本文通过建立神经元模型,分析细胞膜去极化水平及细胞外钾离子浓度的变化对于锋电位波形特征参数的影响。本文主要研究结果如下:(1)HFS期间锋电位幅值显著变小而半高宽增大本文采用降支幅值、升支幅值及半高宽作为表征锋电位波形的特征参数。结果表明,O-HFS期间锋电位发放率升高,并且中间神经元和锥体神经元锋电位幅值显著减小而半高宽显著增加。中间神经元和锥体神经元锋电位降支幅值相对于基线值分别减小20%和30%左右,升支幅值分别可减小40%和20%左右,而半高宽分别增大10%和5%以上。此外A-HFS期间中间神经元锋电位升支幅值减小12%左右,而降支幅值和半高宽的变化与刺激前无显著差异。(2)HFS的兴奋作用是锋电位波形改变的可能机制分析不同刺激频率、不同刺激强度时锋电位波形特征参数的变化,结果发现,具有较高兴奋作用的100 Hz刺激期间锋电位波形特征参数的变化量显著高于200 Hz刺激,而较低强度的HFS期间锋电位波形几乎无变化。此外,在100 Hz的HFS期间,有群峰电位(population spike,PS)时中间神经元锋电位波形的变化更多,降支幅值可减小40%,升支幅值减小55%。,半高宽增大20%。可以推测,HFS对神经元的兴奋作用越大,锋电位波形的变化越多。(3)细胞膜去极化水平的提高和细胞外钾离子浓度的升高影响锋电位波形20 s时长的100Hz的HFS的仿真结果表明,在HFS后期锋电位波形的降支幅值和升支幅值分别减小40%和50%以上,与在体动物实验结果一致。且随着细胞膜去极化水平的提高或细胞外钾离子浓度的升高,锋电位波形的幅值会逐渐减小,并且半高宽增大。可以推测,HFS的作用一方面抬高了神经元的去极化水平,增强了神经元的兴奋性,另一方面引起了钾离子在细胞膜外的积累,使得胞外钾离子浓度升高,进而导致锋电位(即动作电位)波形的改变。总之,本文通过在体动物实验及数学仿真模型的研究发现HFS在增加神经元兴奋性的同时,会改变锋电位的波形,其机制可能是HFS对神经元的兴奋作用抬高了细胞膜的去极化水平,并升高了细胞外钾离子浓度。这些结果为正确跟踪和检测HFS期间神经元的锋电位信号提供了重要信息和依据;并且支持DBS具有兴奋性调制作用的假说,为深入揭示DBS的作用机制提供了重要的线索。
[Abstract]:Deep brain stimulation (DBS) is one of the hot topics in the field of neural engineering. In clinical, the treatment of Parkinson's disease by high frequency electrical stimulation (high frequency stimulation, HFS) in DBS, epilepsy and other brain nervous system diseases has achieved remarkable curative effect, but the mechanism of its action remains controversial. The change of neuronal activity during the period is an important method to reveal the DBS mechanism, and the action potential (front potential) signal of multiple neurons can be recorded simultaneously by microelectrode array technology, which provides important information for the in-depth study of DBS. However, the front potential wave will change during HFS. It is difficult to follow up, and on the other hand it may provide clues to the study of DBS. Therefore, this paper studies the correct heel by applying the 100 Hz or 200 Hz CIS high frequency electrical stimulation (orthodromic-HFS, O-HFS) and reverse high frequency electrical stimulation (antidromic-HFS, A-HFS) on the input and output axons of the hippocampus in the hippocampus of the anesthetized rats. The change of the feature parameters of the front potential wave and its possible mechanism are analyzed by the method of the frontal potential of the trace neuron unit. In addition, in this paper, the effect of the cell membrane depolarization level and the change of the extracellular potassium concentration on the feature parameters of the front potential wave is analyzed by establishing a neuron model. The main research results are as follows: (1) the front power during HFS The amplitudes of the descending branch, the amplitude of the ascending branch and the half width of the height are used as the characteristic parameters of the front potential wave. The results show that the frontal potential distribution is increased during O-HFS, and the amplitude of the frontal potential of the intermediate neurons and pyramidal neurons is significantly reduced, and the half width and width of the middle neuron and the pyramidal God are significantly increased. The amplitude of the descending branch of the descending branch was reduced by 20% and about 30%, respectively, and the amplitude of the ascending branch could be reduced by 40% and 20%, respectively, while the half height width increased by 10% and more than 5%, respectively, and the amplitude of the frontal potential of the middle neuron decreased by 12% during A-HFS, and the amplitude and the half width of the descending branch were not significantly different from those before the stimulation. (2) HFS The exciting effect is the possible mechanism of the change of front potential waveform to analyze the variation of the characteristic parameters of the front potential waveform at different stimulation intensity. The results show that the variation of the feature parameters of the front potential waveform during the 100 Hz stimulation with higher excitation is significantly higher than that of the 200 Hz stimulation, while the front potential waveform of the lower intensity HFS is more than that of the lower intensity. In addition, during the HFS of 100 Hz (population spike, PS), the changes in the frontal potential of the intermediate neurons are more, the amplitude of the descending branch can be reduced by 40%, the amplitude of the ascending branch is reduced by 55%., and the half width and width of 20%. can be increased by 20%., and the greater the excitation of the neuron is, the more changes in the front potential wave. (3) the depolarization of the cell membrane. The increase of level and the increase of extracellular potassium concentration affect the HFS of 100Hz long in the front of the front wave 20 s. The simulation results show that the descending amplitude and the ascending branch amplitude of the front potential wave decrease by 40% and 50% respectively at the later stage of HFS, which are in agreement with the experimental results in vivo, and with the increase of the depolarization level of the cell membrane or the extracellular potassium ionization. The amplitude of the spike potential will gradually decrease and the half width and width increase. It can be speculated that the action of HFS raises the depolarization level of neurons and enhances the excitatory of neurons. On the other hand, the accumulation of potassium ions outside the cell membrane makes the concentration of extracellular potassium increase, which leads to the front potential. In a word, in this paper, we find that HFS can change the waveform of front potential at the same time of increasing the neuron excitability. The mechanism may be that the excitatory action of HFS to neurons elevates the depolarization level of the cell membrane and increases the concentration of extracellular potassium ion. The results provide important information and basis for the correct tracking and detection of the front potential signal of neurons during HFS, and support the hypothesis that DBS has excitatory modulation, which provides an important clue to reveal the mechanism of DBS.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R318.04;TN911.6

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