發(fā)布時(shí)間：2018-06-07 11:40

  本文選題：帕金森病 + 多通道信號(hào)采集��； 參考：《山東師范大學(xué)》2014年碩士論文

【摘要】：實(shí)驗(yàn)?zāi)康模号两鹕。≒arkinson’s Disease，PD）是一種因基底神經(jīng)核環(huán)路中（主要在中腦黑質(zhì)）多巴胺神經(jīng)元缺失或凋亡造成的神經(jīng)系統(tǒng)退行性疾病，經(jīng)黑質(zhì)-紋狀體通路導(dǎo)致紋狀體（Striatum，STR）多巴胺遞質(zhì)缺失的結(jié)果。丘腦束旁核（Parafascicular Nucleus，PF）與基底神經(jīng)節(jié)中的多個(gè)核團(tuán)存在投射關(guān)系，可能在PD病理中起重要作用。本研究通過采集分析PD大鼠PF放電變化以及特定行為時(shí)PD大鼠PF的放電特點(diǎn)。為PD臨床治療的改善提供基礎(chǔ)研究理論依據(jù)。 實(shí)驗(yàn)方法：本課題利用立體定位技術(shù)，通過直接腦內(nèi)靶位點(diǎn)注射的方法，在大鼠中腦腹側(cè)被蓋區(qū)（Ventra TegmentalArea，VTA）和黑質(zhì)致密部（Substantia Nigra pars Compacta，SNc）分別注射2μL和3μL的6-羥基多巴胺（6-hydroxydopamine，6-OHDA）建立PD動(dòng)物模型。在正常和PD大鼠腦PF內(nèi)植入自制多通道電極陣列，通過美國Plexon公司生產(chǎn)的多通道信號(hào)采集儀采集記錄大鼠PF鋒電位和局部場電位（Local Field Potentials，LFPs）信號(hào)。對采集的PD大鼠清醒安靜狀態(tài)和抓區(qū)食物時(shí)PF的鋒電位和LFPs信號(hào)進(jìn)行用OfflineSorter、Neuroexplorer和Matlab分析。最后藍(lán)點(diǎn)實(shí)驗(yàn)和中性紅染色鑒定位點(diǎn)準(zhǔn)確性，以及免疫組織化學(xué)觀察黑質(zhì)損毀情況。 實(shí)驗(yàn)結(jié)果：用Offline Sorter軟件將采集到的鋒電位信號(hào)進(jìn)行分類，根據(jù)波形、時(shí)程、放電模式主成分分析（Principal Component Analysis，PCA）等諸多特征數(shù)據(jù)，將PF神經(jīng)元分為兩類：神經(jīng)元類型A，特點(diǎn)是波峰高，時(shí)程長，放電節(jié)律不規(guī)則；神經(jīng)元類型B，特點(diǎn)是波峰平緩，時(shí)程短，放電節(jié)律相對規(guī)則。用Neuroexplorer分析顯示，在清醒靜止?fàn)顟B(tài)下，對照組與PD組大鼠兩種神經(jīng)元放電率沒有發(fā)生顯著差異，與對照組大鼠比較，神經(jīng)元類型A的放電模式由不規(guī)律變得較為規(guī)律；PD組中神經(jīng)元類型B放電模式變得不規(guī)律。將LFPs數(shù)據(jù)導(dǎo)入Matlab進(jìn)行分析，PD組大鼠PF的LFPs在0.7~20Hz的頻段信號(hào)頻率低于對照組大鼠；但20~40Hz頻段信號(hào)的頻率高于對照組大鼠。通過時(shí)頻圖可以直觀的反應(yīng)能量分布情況，該結(jié)果與頻段分析所得結(jié)果基本相符。PD大鼠抓食運(yùn)動(dòng)時(shí)PF神經(jīng)元放電變化結(jié)果顯示，PD組大鼠抓食動(dòng)作所需時(shí)間明顯長于對照組大鼠。Neuroexplorer導(dǎo)出數(shù)據(jù)統(tǒng)計(jì)學(xué)處理顯示，PD大鼠PF兩種神經(jīng)元的放電率均顯著降低；放電間隔直方圖的變異系數(shù)（Interspike Interval of Coefficient of Variation，Coeff. Var. ISI）僅神經(jīng)元類型B顯著增高，神經(jīng)元類型A僅有增大趨勢而無顯著差異。Matlab進(jìn)行LFPs分析，PD組大鼠PF的LFPs在0.7~20Hz頻段的信號(hào)明顯低于對照組大鼠，PD組大鼠40~100Hz頻段信號(hào)百分比高于對照組大鼠。 結(jié)論：PF神經(jīng)元分為兩類。清醒靜止情況下，PD大鼠PF鋒電位的放電率并未發(fā)生顯著變化，但是放電模式產(chǎn)生顯著差異；PD大鼠PF的LFPs在0.7~20Hz頻段頻率顯著降低，20~40Hz頻段頻率有顯著升高。抓食行為下，PD大鼠PF鋒電位的放電率顯著降低，放電模式產(chǎn)生變化。PD大鼠PF的LFPs在0.7~20Hz頻段頻率顯著降低，40~100Hz頻段頻率顯著升高。在特定行為下，PD大鼠PF鋒電位及LFPs均產(chǎn)生了變化，說明PF與丘腦-皮層環(huán)路之間存在聯(lián)系。從電生理角度，，為PF成為新的PD治療靶位點(diǎn)提供理論基礎(chǔ)。
[Abstract]:Objective: Parkinson's disease (Parkinson 's Disease, PD) is a result of the neurodegenerative disease caused by the deletion or apoptosis of dopamine neurons in the basal ganglia (mainly in the mesencephalic substantia nigra), resulting in the loss of dopamine transmitters in the striatum (Striatum, STR) through the substantia nigrostriatal pathway. The paramparo nucleus of the thalamus (Parafascicular N). Ucleus, PF) has a projective relationship with multiple nuclei in the basal ganglia, and may play an important role in the pathology of PD. This study provides a basic theoretical basis for the improvement of the clinical treatment of PD by collecting and analyzing the changes of PF discharge in PD rats and the discharge characteristics of PF in PD rats when specific behaviors.
Experimental methods: using stereotaxic technique and injecting direct target loci in the brain, Ventra TegmentalArea (VTA) and Substantia Nigra pars Compacta, SNc (Substantia Nigra pars Compacta, SNc) were injected into the rat model of 6- hydroxy dopamine (6-hydroxydopamine), respectively, in the mesencephalic ventral tegmental area (VTA) and the dense Substantia Nigra pars Compacta (SNc). The self-made multi-channel electrode array was implanted in the PF of PD rat brain, and the PF front potential and local field potential (Local Field Potentials, LFPs) signal were collected and recorded by the multi-channel signal acquisition instrument produced by Plexon company in the United States. The front and LFPs signals of PF in the sober and quiet state of the collected PD rats and the grabbing food were used for OfflineSort. Er, Neuroexplorer and Matlab analysis. Finally, the blue dot test and neutral red staining were used to identify the location of the lesion, and immunohistochemistry to observe the lesion of substantia nigra.
Experimental results: Offline Sorter software is used to classify the collected front potential signals. According to the waveform, time history, Principal Component Analysis, PCA, and many other characteristic data, PF neurons are divided into two categories: neuron type A, characterized by high wave peak, long duration, irregular discharge rhythm, and neuronal type B The discharge rate of two kinds of neurons in the control group and the PD group had no significant difference between the control group and the PD group. The discharge mode of the neuron type A became more regular, and the neuron type B in the PD group was B. The discharge mode became irregular. The LFPs data was introduced into Matlab for analysis. The frequency of LFPs in the PF of group PD rats was lower than that of the control group, but the frequency of the 20~40Hz band signal was higher than that of the control group. The time frequency map could directly respond to the distribution of energy, and the results were basically consistent with the results obtained from the analysis of the frequency band. The results of the discharge changes of PF neurons in the PD rats showed that the time needed for the grab action of the rats in the group PD was longer than that of the control group, and the data of the.Neuroexplorer derived data from the control group showed that the discharge rate of the PF two neurons in the PD rats decreased significantly, and the variation coefficient of the histogram of the discharge interval (Interspike Interval of Coefficient of) Variation, Coeff. Var. ISI) significantly increased the neuron type B, and the neuron type A only increased with no significant difference in.Matlab for LFPs analysis. The LFPs of PF in the PD group rats was significantly lower than that of the control rats. The percentage of the frequency bands of the frequency band of the rats was higher than that of the control group.
Conclusion: PF neurons were divided into two types. The discharge rate of PF front potential in PD rats did not change significantly, but the discharge patterns were significantly different. The LFPs of PF in PD rats decreased significantly in the 0.7~20Hz band frequency, and the frequency of 20~40Hz band increased significantly. The discharge rate of PF front potential of PD rats decreased significantly. The LFPs of PF in.PD rats decreased significantly at the frequency of 0.7~20Hz band, and the frequency of 40~100Hz band increased significantly. Under specific behavior, the PF front potential and LFPs of PD rats were changed, indicating the relationship between PF and the thalamus cortical loop. From the electrophysiological point of view, it provided a theoretical basis for PF to become a new PD therapeutic target site.
【學(xué)位授予單位】：山東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R742.5

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