帕金森病大鼠在特定运动状态下GPe和GPi电生理学特征变化及相关性分析

发布时间：2018-06-21 18:29

本文选题：帕金森病 + 动作电位　；参考：《山东师范大学》2016年硕士论文

【摘要】：帕金森病(Parkinson’s disease,PD)病变的主要部位在中脑黑质和基底神经节。在基底神经节中,苍白球外侧部(globus pallidus external segment,GPe)是重要的中继核团,苍白球内侧部(globus pallidus internal segment,GPi)是主要的输出核团。研究目的:本研究旨在探究PD大鼠GPe、GPi电生理学特征的变化以及两个核团之间局部场电位(local field potential,LFP)相关性的变化,包括:1、对PD大鼠运动障碍进行量化测评。2、探究PD大鼠在清醒静止和连续运动两种状态下GPe、GPi动作电位和LFP的变化。3、探究PD大鼠GPe与GPi之间LFP相关性的变化。研究方法:建立PD大鼠模型,通过大鼠脑立体定位手术,将两束电极阵列分别植入同一只PD大鼠GPe、GPi内,使用Plexon多通道信号采集系统采集PD大鼠在清醒静止和连续运动两种状态下的动作电位和LFP。将采集到的动作电位导入Offline Sorter软件进行聚类分析,使用Neuro Explorer软件分析每类神经元放电率和放电模式的变化;将采集到的LFP导入Matlab,使用LFP Analysis Software 2009软件分析每个核团时频、功率谱密度和频段分布的变化,使用LFP Analysis Software 2009软件和Chronux软件分析两个核团之间LFP相关性的变化,包括交叉相关分析和一致性分析。研究结果:1、行为学量化测评结果PD大鼠运动障碍测评结果:与正常大鼠相比,PD大鼠在跑步机上的最长运动时间(min)变短(20 r/min:18.00±2.74 vs 26.98±0.91,P=0.03;30 r/min:3.33±1.45 vs 26.67±0.71,P0.01),步频(steps/min)降低(20 r/min:73.33±7.00 vs 95.50±4.94,P=0.04;30 r/min:76.33±7.41 vs110.33±7.58,P0.01),失误次数(times)增多(9 r/min:1.50±0.55 vs 0.67±0.33,P=0.04;15 r/min:2.50±0.76 vs 0.83±0.48,P=0.04;20 r/min:7.50±0.76 vs 1.50±0.43,P0.01;30 r/min:10.00±0.00 vs 2.00±0.58,P0.01)。跑步机转速筛选结果:在12 r/min时,两组大鼠不连续运动频率均较低,适宜采集大鼠在连续运动状态下的脑电信号。2、GPe动作电位分析结果GPe根据放电率和放电模式分为伴随暂停的高频率放电(high frequency pausers,HFP)和伴随爆发的低频率放电(low frequency bursters,LFB)两类神经元。在清醒静止和连续运动两种状态下,与正常大鼠相比,PD大鼠HFP放电率(spikes/s)降低(静止:11.89±0.98 vs18.63±1.50,P0.01;运动:16.08±1.51 vs 23.25±1.27,P0.01),变异系数(coefficient of variation,CV)值增大(静止:1.06±0.05 vs 0.72±0.04,P0.01;运动:1.33±0.03 vs 1.00±0.03,P0.01);PD大鼠LFB放电率降低(静止:6.11±0.39 vs 10.33±0.79,P0.01;运动:10.18±0.51vs 13.15±0.66,P0.01),CV值增大(静止:2.31±0.23 vs 1.54±0.08,P0.01;运动:2.48±0.21vs 1.62±0.15,P0.01)。与清醒静止状态相比,在连续运动状态下,正常大鼠和PD大鼠HFP放电率升高(正常:23.25±1.27 vs 18.63±1.50,P=0.03;PD:16.08±1.51 vs 11.89±0.98,P=0.03),CV值增大(正常:1.00±0.03 vs 0.72±0.04,P0.01;PD:1.33±0.03 vs 1.06±0.05,P0.01);LFB放电率升高(正常:13.15±0.66 vs 10.33±0.79,P=0.01;PD:10.18±0.51 vs 6.11±0.39,P0.01)。3、GPi动作电位分析结果GPi只有一类神经元。在清醒静止和连续运动两种状态下,与正常大鼠相比,PD大鼠GPi放电率升高(静止:27.05±1.66 vs 23.18±1.25,P0.01;运动:29.93±0.68 vs 25.16±0.65,P0.01),CV值增大(静止:1.04±0.08 vs 0.72±0.03,P0.01;运动:1.12±0.04 vs 0.89±0.03,P0.01)。与清醒静止状态相比,在连续运动状态下,正常大鼠和PD大鼠GPi放电率升高(正常:25.16±0.65 vs 23.18±1.25,P=0.03;PD:29.93±0.68 vs 27.05±1.66,P0.01),CV值增大(正常:0.89±0.03 vs 0.72±0.03,P0.01;PD:1.12±0.04 vs 1.04±0.08,P=0.03)。4、PD大鼠GPe、GPi局部场电位分析结果在清醒静止状态下,与正常大鼠相比,PD大鼠GPe、GPi的LFP在0.5~12 Hz频段的能量占总能量(0.5~200 Hz频段的能量)的百分比降低(GPe:59.27±3.28 vs 74.44±1.68,P0.01;GPi:67.99±1.60 vs 80.88±1.80,P0.01),在12~35 Hz频段的能量占总能量的百分比升高(GPe:28.32±1.94 vs 18.74±1.54,P0.01;GPi:26.32±2.16 vs 11.45±1.07,P0.01)。在连续运动状态下,与正常大鼠相比,PD大鼠GPe、GPi的LFP在0.5~12 Hz频段的能量占总能量的百分比降低(GPe:66.76±1.83 vs 79.11±2.80,P0.01;GPi:62.69±1.79 vs 76.79±1.19,P0.01),在12~35 Hz频段的能量占总能量的百分比升高(GPe:24.53±1.64 vs13.65±1.91,P0.01;GPi:27.15±1.51 vs 16.10±0.80,P0.01),在35~70 Hz频段的能量占总能量的百分比升高(GPe:3.03±0.48 vs 1.07±0.46,P=0.04;GPi:4.77±0.65 vs 2.03±0.34,P0.01)。5、PD大鼠GPe与GPi之间LFP相关性分析结果与正常大鼠相比,PD大鼠GPe与GPi之间LFP在0.5~12 Hz和12~35 Hz频段的最大交叉相关系数增大(0.5~12 Hz:0.81±0.02 vs 0.37±0.03,P0.01;12~35 Hz:0.81±0.03 vs0.43±0.07,P0.01),平均相位一致性值增大(0.5~12 Hz:0.69±0.03 vs 0.25±0.01,P0.01;12~35 Hz:0.73±0.04 vs 0.30±0.06,P0.01)。研究结论:行为学量化测评实验结果显示,PD大鼠出现运动障碍,表现为运动协调性差,尤其对高转速控制能力差;12 r/min适宜大鼠在跑步机上连续运动。电生理学实验结果显示,PD大鼠GPe神经元放电率降低,GPi神经元放电率升高;二者CV值都增大,表明放电规则性降低,放电模式发生变化。PD大鼠GPe、GPi的LFP在0.5~12 Hz频段的能量降低,在12~35 Hz频段的能量升高。PD大鼠GPe与GPi之间LFP在0.5~12 Hz和12~35Hz频段的同步性都增强。与此同时,在连续运动状态下,GPe和GPi神经元放电率升高,CV值增大,提示GPe、GPi与运动相关。
[Abstract]:The main site of the disease of Parkinson's disease (Parkinson 's disease, PD) is in the mesencephalic substantia nigra and basal ganglia. In the basal ganglia, the lateral part of the globus pallidus (globus pallidus external segment, GPe) is an important relay nucleus. The main output nucleus is the medial part of the globus pallidus (globus pallidus internal). The purpose of this study was to explore the changes in the electrophysiological characteristics of GPe and GPi in PD rats and the changes in the correlation between the local field potential (local field potential, LFP) between the two nuclei, including: 1. The quantitative measurement of the dyskinesia of PD rats was carried out, and the GPe in the two states of awake and continuous movement of PD rats was explored. The change of LFP correlation between rat GPe and GPi. Research methods: establish a PD rat model. Through the stereotaxic operation of the rat brain, the two beam electrode arrays were implanted into the same PD rat GPe, GPi, and the Plexon multichannel signal acquisition system was used to collect the action potential and LFP. of PD rats in two states of sober rest and continuous motion. The action potential is introduced into Offline Sorter software for clustering analysis, and Neuro Explorer software is used to analyze the variation of discharge rate and discharge mode of each type of neuron; the collected LFP is introduced into Matlab, and LFP Analysis Software 2009 software is used to analyze the time frequency, power spectral density and frequency distribution of each nucleus, and LFP Analysis So. Ftware 2009 software and Chronux software analyzed the changes of LFP correlation between two nuclear groups, including cross correlation analysis and consistency analysis. Results: 1, the results of PD rats were measured by behavioral quantification: compared with normal rats, the longest movement time (min) on the treadmill of PD rats was shorter (20 r/min:18.00 + 2.74 VS). 26.98 + 0.91, P=0.03, 30 r/min:3.33 + 1.45 vs 26.67 + 0.71, P0.01), the step frequency (steps/min) decreased (20 r/min:73.33 + 7 vs 95.50 + 4.94, P=0.04; 30 r/min:76.33 + 7.41 vs110.33 +% 7.58, P0.01), and the number of turnovers (Times) increased S 1.50 + 0.43, P0.01, 30 r/min:10.00 + 0 vs 2 + 0.58, P0.01). The result of the treadmill speed screening: at 12 r/min, the discontinuous motion frequency of the two groups of rats is low. It is suitable to collect the electroencephalogram.2 of the rat in the continuous motion state, and the result of GPe action potential analysis is divided into the high frequency with the discharge rate and the discharge mode. The discharge (high frequency pausers, HFP) and the low frequency discharge (low frequency bursters, LFB) two types of neurons with the outburst. In two states of sober rest and continuous motion, the HFP discharge rate (spikes/s) of the PD rats is lower than that of the normal rats (11.89 + 0.98 vs18.63 1.50, 16.08 + 1.51 23.25 + 1.27.) The value of coefficient of variation (CV) increased (still: 1.06 + 0.05 vs 0.72 + 0.04, P0.01; movement: 1.33 + 0.03 vs 1 + 0.03, P0.01); LFB discharge rate of PD rats decreased (still: 6.11 + 0.39 vs 10.33 + 0.79, P0.01. S 1.62 + 0.15, P0.01). Compared with the state of sober rest, the rate of HFP discharge in normal rats and PD rats increased (normal: 23.25 + 1.27 vs 18.63 + 1.50, P=0.03; PD:16.08 + 1.51 vs 11.89 + 0.98, P=0.03), and CV value increased (1 + 0.03 vs 0.72 + 0.04, P0.01. Normal: 13.15 + 0.66 vs 10.33 + 0.79, P=0.01, PD:10.18 + 0.51 vs 6.11 + 0.39, P0.01).3, GPi action potential analysis showed that GPi had only one class of neurons. In two states of sober rest and continuous movement, the GPi discharge rate of PD rats increased (still: 27.05 + 1.66 vs 23.18 + 1.25, P0.01) P0.01), the value of CV increased (still: 1.04 + 0.08 vs 0.72 + 0.03, P0.01; movement: 1.12 + 0.04 vs 0.89 + 0.03, P0.01). The rate of GPi discharge in normal rats and PD rats increased (normal: 25.16 + 0.65 vs 23.18 + 1.25, P=0.03; PD:29.93 + 0.68 VS). Vs 0.72 + 0.03, P0.01; PD:1.12 + 0.04 vs 1.04 + 0.08, P=0.03).4, PD rat GPe, GPi local field potential analysis results in sober rest state, PD rat GPe, GPi's energy accounted for the percentage of total energy (3.28 74.44 + 1.68). 9 + 1.60 vs 80.88 + 1.80, P0.01), the percentage of energy in the 12~35 Hz band increased (GPe:28.32 1.94 vs 18.74 + 1.54, P0.01; GPi:26.32 + 2.16 vs 11.45 + 1.07, P0.01). 1.83 vs 79.11 + 2.80, P0.01, GPi:62.69 + 1.79 vs 76.79 + 1.19, P0.01), the percentage of energy in the 12~35 Hz band increased (GPe:24.53 + 1.64 vs13.65 + 1.91, P0.01; GPi:27.15 + 1.51 vs 16.10 + 0.80,). .65 vs 2.03 + 0.34, P0.01).5, LFP correlation analysis between GPe and GPi in PD rats compared with normal rats, the maximum cross correlation coefficient of GPe and GPi between GPe and GPi in PD rats increased. 5~12 Hz:0.69 + 0.03 vs 0.25 + 0.01, P0.01; 12~35 Hz:0.73 + 0.04 vs 0.30 + 0.06, P0.01). Conclusion: the experimental results of quantitative behavior test showed that the dyskinesia was poor in the PD rats, especially for high speed control, and 12 r/min was suitable for the rats on the treadmill. The discharge rate of GPe neurons in PD rats decreased and the discharge rate of GPi neurons increased, and the two CV values increased, indicating that the discharge rule was reduced, the discharge mode changed in.PD rats GPe, the energy of GPi LFP in the 0.5~12 Hz band was reduced, and the synchronicity of the energy increase between the 12~35 Hz frequency band and the frequency segment of the 12~35 Hz band was both. At the same time, in continuous motion, the firing rate of GPe and GPi neurons increased and CV increased, suggesting that GPe and GPi were related to exercise.
【学位授予单位】：山东师范大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R742.5

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