本文選題：高頻電刺激(HFS) + 海馬CA1區(qū)�。� 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：深部腦刺激(deep brain stimulation,DBS)是神經(jīng)工程領(lǐng)域的研究熱點之一。臨床上,利用DBS中的高頻電刺激(high frequency stimulation,HFS)治療帕金森氏癥、癲癇等腦神經(jīng)系統(tǒng)疾病已經(jīng)取得了令人矚目的療效,但其作用機制依然存在爭議。研究電刺激期間神經(jīng)元活動的變化是揭示DBS機制的重要方法,而利用微電極陣列技術(shù)可以在細(xì)胞外同時記錄多個神經(jīng)元的動作電位(即鋒電位)信號,為DBS的深入研究提供重要信息。但是,HFS期間鋒電位波形會產(chǎn)生變化,這一方面給鋒電位的檢測和跟蹤造成了困難,另一方面也可能為研究DBS提供線索。因此,本文通過麻醉大鼠的在體實驗,在海馬CA1區(qū)輸入及輸出軸突上施加1～2 min時長的100 Hz或200 Hz順向高頻電刺激(orthodromic-HFS,O-HFS)和逆向高頻電刺激(antidromic-HFS,A-HFS),研究正確跟蹤神經(jīng)元單元鋒電位的方法,分析鋒電位波形特征參數(shù)的變化及其可能機制。此外,本文通過建立神經(jīng)元模型,分析細(xì)胞膜去極化水平及細(xì)胞外鉀離子濃度的變化對于鋒電位波形特征參數(shù)的影響。本文主要研究結(jié)果如下:(1)HFS期間鋒電位幅值顯著變小而半高寬增大本文采用降支幅值、升支幅值及半高寬作為表征鋒電位波形的特征參數(shù)。結(jié)果表明,O-HFS期間鋒電位發(fā)放率升高,并且中間神經(jīng)元和錐體神經(jīng)元鋒電位幅值顯著減小而半高寬顯著增加。中間神經(jīng)元和錐體神經(jīng)元鋒電位降支幅值相對于基線值分別減小20%和30%左右,升支幅值分別可減小40%和20%左右,而半高寬分別增大10%和5%以上。此外A-HFS期間中間神經(jīng)元鋒電位升支幅值減小12%左右,而降支幅值和半高寬的變化與刺激前無顯著差異。(2)HFS的興奮作用是鋒電位波形改變的可能機制分析不同刺激頻率、不同刺激強度時鋒電位波形特征參數(shù)的變化,結(jié)果發(fā)現(xiàn),具有較高興奮作用的100 Hz刺激期間鋒電位波形特征參數(shù)的變化量顯著高于200 Hz刺激,而較低強度的HFS期間鋒電位波形幾乎無變化。此外,在100 Hz的HFS期間,有群峰電位(population spike,PS)時中間神經(jīng)元鋒電位波形的變化更多,降支幅值可減小40%,升支幅值減小55%。,半高寬增大20%�？梢酝茰y,HFS對神經(jīng)元的興奮作用越大,鋒電位波形的變化越多。(3)細(xì)胞膜去極化水平的提高和細(xì)胞外鉀離子濃度的升高影響鋒電位波形20 s時長的100Hz的HFS的仿真結(jié)果表明,在HFS后期鋒電位波形的降支幅值和升支幅值分別減小40%和50%以上,與在體動物實驗結(jié)果一致。且隨著細(xì)胞膜去極化水平的提高或細(xì)胞外鉀離子濃度的升高,鋒電位波形的幅值會逐漸減小,并且半高寬增大�？梢酝茰y,HFS的作用一方面抬高了神經(jīng)元的去極化水平,增強了神經(jīng)元的興奮性,另一方面引起了鉀離子在細(xì)胞膜外的積累,使得胞外鉀離子濃度升高,進(jìn)而導(dǎo)致鋒電位(即動作電位)波形的改變�？傊�,本文通過在體動物實驗及數(shù)學(xué)仿真模型的研究發(fā)現(xiàn)HFS在增加神經(jīng)元興奮性的同時,會改變鋒電位的波形,其機制可能是HFS對神經(jīng)元的興奮作用抬高了細(xì)胞膜的去極化水平,并升高了細(xì)胞外鉀離子濃度。這些結(jié)果為正確跟蹤和檢測HFS期間神經(jīng)元的鋒電位信號提供了重要信息和依據(jù);并且支持DBS具有興奮性調(diào)制作用的假說,為深入揭示DBS的作用機制提供了重要的線索。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R318.04;TN911.6

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 封洲燕;肖乾江;胡振華;;電刺激期間神經(jīng)細(xì)胞單元鋒電位的檢測[J];中國生物醫(yī)學(xué)工程學(xué)報;2013年04期

2 封洲燕;王靜;汪洋;鄭曉靜;;神經(jīng)元鋒電位信號濾波頻率的選擇[J];浙江大學(xué)學(xué)報(工學(xué)版);2012年02期

3 王靜;封洲燕;;多通道神經(jīng)元鋒電位檢測和分類的新方法[J];生物化學(xué)與生物物理進(jìn)展;2009年05期

4 封洲燕;王靜;;微電極陣列大腦電信號檢測技術(shù)的進(jìn)展[J];電子學(xué)報;2009年01期

5 封洲燕;光磊;鄭曉靜;王靜;李淑輝;;應(yīng)用線性硅電極陣列檢測海馬場電位和單細(xì)胞動作電位[J];生物化學(xué)與生物物理進(jìn)展;2007年04期

，

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