帕金森病大鼠丘脑束旁核电信号研究

发布时间：2018-06-07 11:40

本文选题：帕金森病 + 多通道信号采集　；参考：《山东师范大学》2014年硕士论文

【摘要】：实验目的：帕金森病（Parkinson’s Disease，PD）是一种因基底神经核环路中（主要在中脑黑质）多巴胺神经元缺失或凋亡造成的神经系统退行性疾病，经黑质-纹状体通路导致纹状体（Striatum，STR）多巴胺递质缺失的结果。丘脑束旁核（Parafascicular Nucleus，PF）与基底神经节中的多个核团存在投射关系，可能在PD病理中起重要作用。本研究通过采集分析PD大鼠PF放电变化以及特定行为时PD大鼠PF的放电特点。为PD临床治疗的改善提供基础研究理论依据。实验方法：本课题利用立体定位技术，通过直接脑内靶位点注射的方法，在大鼠中脑腹侧被盖区（Ventra TegmentalArea，VTA）和黑质致密部（Substantia Nigra pars Compacta，SNc）分别注射2μL和3μL的6-羟基多巴胺（6-hydroxydopamine，6-OHDA）建立PD动物模型。在正常和PD大鼠脑PF内植入自制多通道电极阵列，通过美国Plexon公司生产的多通道信号采集仪采集记录大鼠PF锋电位和局部场电位（Local Field Potentials，LFPs）信号。对采集的PD大鼠清醒安静状态和抓区食物时PF的锋电位和LFPs信号进行用OfflineSorter、Neuroexplorer和Matlab分析。最后蓝点实验和中性红染色鉴定位点准确性，以及免疫组织化学观察黑质损毁情况。实验结果：用Offline Sorter软件将采集到的锋电位信号进行分类，根据波形、时程、放电模式主成分分析（Principal Component Analysis，PCA）等诸多特征数据，将PF神经元分为两类：神经元类型A，特点是波峰高，时程长，放电节律不规则；神经元类型B，特点是波峰平缓，时程短，放电节律相对规则。用Neuroexplorer分析显示，在清醒静止状态下，对照组与PD组大鼠两种神经元放电率没有发生显著差异，与对照组大鼠比较，神经元类型A的放电模式由不规律变得较为规律；PD组中神经元类型B放电模式变得不规律。将LFPs数据导入Matlab进行分析，PD组大鼠PF的LFPs在0.7~20Hz的频段信号频率低于对照组大鼠；但20~40Hz频段信号的频率高于对照组大鼠。通过时频图可以直观的反应能量分布情况，该结果与频段分析所得结果基本相符。PD大鼠抓食运动时PF神经元放电变化结果显示，PD组大鼠抓食动作所需时间明显长于对照组大鼠。Neuroexplorer导出数据统计学处理显示，PD大鼠PF两种神经元的放电率均显著降低；放电间隔直方图的变异系数（Interspike Interval of Coefficient of Variation，Coeff. Var. ISI）仅神经元类型B显著增高，神经元类型A仅有增大趋势而无显著差异。Matlab进行LFPs分析，PD组大鼠PF的LFPs在0.7~20Hz频段的信号明显低于对照组大鼠，PD组大鼠40~100Hz频段信号百分比高于对照组大鼠。结论：PF神经元分为两类。清醒静止情况下，PD大鼠PF锋电位的放电率并未发生显著变化，但是放电模式产生显著差异；PD大鼠PF的LFPs在0.7~20Hz频段频率显著降低，20~40Hz频段频率有显著升高。抓食行为下，PD大鼠PF锋电位的放电率显著降低，放电模式产生变化。PD大鼠PF的LFPs在0.7~20Hz频段频率显著降低，40~100Hz频段频率显著升高。在特定行为下，PD大鼠PF锋电位及LFPs均产生了变化，说明PF与丘脑-皮层环路之间存在联系。从电生理角度，，为PF成为新的PD治疗靶位点提供理论基础。
[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.
【学位授予单位】：山东师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

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