【摘要】：本研究采用6-羥基多巴胺(6-hydroxydopamine,6-OHDA)建立帕金森病(Parkinson’s disease,PD)大鼠模型。通過多通道在體記錄技術(shù),記錄在清醒靜止和特定抓食運(yùn)動(dòng)狀態(tài)下大鼠底丘腦核(subthalamic nucleus,STN)和初級(jí)運(yùn)動(dòng)皮質(zhì)(primary motor cortex,M1)神經(jīng)元的放電變化,包括鋒電位(spikes)和局部場電位(local field potential,LFPs)兩部分。用Offline Sorter和Neuro Explorer軟件還有Matlab軟件分析實(shí)驗(yàn)組大鼠和對照組大鼠STN和M1腦區(qū)內(nèi)神經(jīng)元的電生理變化以及二者的相互關(guān)系。實(shí)驗(yàn)?zāi)康?為深入探索PD的發(fā)病機(jī)理并找到更快更有效的治療方法提供理論基礎(chǔ)。實(shí)驗(yàn)結(jié)果:根據(jù)神經(jīng)元放電模式、放電頻率等指標(biāo),將采集到的STN核團(tuán)的電信號(hào)分為兩種類型。在清醒靜止?fàn)顟B(tài)下,實(shí)驗(yàn)組大鼠的第II類神經(jīng)元的放電頻率(Hz)(4.29±0.87)比對照組大鼠(2.97±0.20)顯著升高,實(shí)驗(yàn)組大鼠的第II類神經(jīng)元CV(coefficient of variation)值(1.06±0.04)比對照組大鼠(0.95±0.01)顯著增加;在特定抓食運(yùn)動(dòng)狀態(tài)下,實(shí)驗(yàn)組大鼠的第II類神經(jīng)元放電頻率(Hz)(18.64±0.35)比對照組大鼠的第II類神經(jīng)元放電頻率(14.07±1.16)顯著升高,而第I類神經(jīng)元無顯著變化。在清醒靜止?fàn)顟B(tài)下,局部場電位信號(hào)各頻段能量所占百分比發(fā)生顯著變化,其中實(shí)驗(yàn)組大鼠在0.7~12Hz頻段的能量占0.7~200Hz頻段的百分比(70.66±0.73)較對照組大鼠(80.75±2.35)顯著降低,其他頻段所占百分比顯著升高。在特定抓食運(yùn)動(dòng)狀態(tài)下,實(shí)驗(yàn)組大鼠局部場電位在0.7~12Hz頻段的能量占0.7~200Hz頻段的百分比(65.27±1.48)較對照組大鼠(73.85±1.73)顯著降低,實(shí)驗(yàn)組大鼠在12~35Hz頻段能量所占百分比(21.92±0.80)較對照組大鼠(13.95±1.56)顯著升高,其他頻段的能量所占的百分比無明顯變化。對記錄到的M1核團(tuán)進(jìn)行神經(jīng)元分類,得到兩類神經(jīng)元,分別為中間神經(jīng)元和錐體神經(jīng)元。在清醒靜止?fàn)顟B(tài)下,實(shí)驗(yàn)組大鼠錐體神經(jīng)元的放電頻率(Hz)(3.11±0.47)比對照組大鼠(4.23±0.70)顯著降低,實(shí)驗(yàn)組大鼠錐體神經(jīng)元的CV值(0.92±0.03)比對照組大鼠(0.97±0.03)顯著減小,而中間神經(jīng)元電生理活動(dòng)無顯著變化;在特定抓食運(yùn)動(dòng)狀態(tài)下,實(shí)驗(yàn)組大鼠錐體神經(jīng)元的放電頻率(Hz)(11.55±0.39)比對照組大鼠(16.70±1.00)顯著降低,實(shí)驗(yàn)組大鼠中間神經(jīng)元的放電頻率(Hz)(17.36±1.59)較對照組大鼠(28.49±1.18)顯著降低。在清醒靜止?fàn)顟B(tài)下局部場電位信號(hào),實(shí)驗(yàn)組大鼠在0.7~12Hz頻段能量占0.7~200Hz頻段總能量的百分比(54.65±3.17)較對照組大鼠(73.29±1.32)顯著降低,實(shí)驗(yàn)組大鼠在12~35Hz頻段能量所占總能量的百分比(28.85±2.23)較對照組大鼠(17.66±0.51)顯著升高,其他頻段所占的百分比無明顯變化;在特定抓食運(yùn)動(dòng)狀態(tài)下,局部場電位信號(hào)實(shí)驗(yàn)組大鼠在0.7~12Hz頻段能量占0.7~200Hz頻段總能量的百分比(41.14±1.30)較對照組大鼠(49.15±2.40)顯著降低,12~35Hz頻段能量占總能量的百分比(24.44±1.63)較對照組大鼠(19.47±0.82)顯著升高,其他頻段能量所占的百分比無明顯變化。對相同時(shí)間段內(nèi)記錄的STN和M1的局部場電位信號(hào)進(jìn)行相關(guān)性分析,得出實(shí)驗(yàn)組大鼠的相關(guān)系數(shù)在0.7~12 Hz頻段(0.52±0.02)比對照組大鼠(0.44±0.02)顯著升高,在12~35 Hz頻段實(shí)驗(yàn)組大鼠的相關(guān)系數(shù)(0.49±0.02)比對照組大鼠(0.40±0.01)顯著升高。平均相位一致性與相關(guān)系數(shù)有相似的結(jié)果:0.7~12 Hz頻段實(shí)驗(yàn)組大鼠的平均相位一致性(0.59±0.02)比對照組大鼠(0.52±0.02)顯著升高,在12~35 Hz頻段實(shí)驗(yàn)組大鼠的平均相位一致性(0.51±0.03)比對照組大鼠(0.41±0.02)顯著升高。實(shí)驗(yàn)結(jié)論:PD大鼠STN和M1核團(tuán)的神經(jīng)元單細(xì)胞放電和LFPs都發(fā)生顯著變化,而且兩個(gè)核團(tuán)的相關(guān)性也增加,推測這兩個(gè)腦區(qū)之間存在重要的纖維投射,為治療帕金森病提供理論依據(jù)。
[Abstract]:In this study, 6-hydroxydopamine (6-OHDA) was used to establish a rat model of Parkinson's disease (PD). Neurons in subthalamic nucleus (STN) and primary motor cortex (M1) were recorded by multi-channel in vivo recording technique during waking, resting and specific grazing exercise in rats. The electrophysiological changes of neurons in STN and M1 brain regions of experimental and control rats were analyzed by Offline Sorter, Neuro Explorer and MATLAB software. The results showed that the electrical signals of STN nuclei were divided into two types according to neuronal discharge patterns and discharge frequencies. The CV (coefficient of variation) of type II neurons in the experimental group was significantly higher than that in the control group (0.95+0.01), and the firing frequency (Hz) (18.64+0.35) of type II neurons in the experimental group was significantly higher than that in the control group (14.07+1.05). The percentage of energy in each frequency band of the local field potential signal changed significantly in the waking and resting state. The percentage of energy in the 0.7-12 Hz band of the experimental group in the 0.7-200 Hz band (70.66.73) was significantly lower than that in the control group (80.75 The percentage of local field potential energy in 0.7-12 Hz band (65.27+1.48) in the experimental group was significantly lower than that in the control group (73.85+1.73), and the percentage of energy in 12-35 Hz band (21.92+0.80) in the experimental group was significantly lower than that in the control group (13.95+1.56). Two types of neurons, intermediate neurons and pyramidal neurons, were obtained by classifying the recorded M1 nuclei. The firing frequency of pyramidal neurons in the experimental group (Hz) (3.11 + 0.47) was significantly lower than that in the control group (4.23 + 0.70). The CV value of pyramidal neurons in the experimental group (0.92.03) was significantly lower than that in the control group (0.97.03), but the electrophysiological activity of the intermediate neurons was not significantly changed. The firing frequency (Hz) (11.55.39) of pyramidal neurons in the experimental group was significantly lower than that in the control group (16.70.00), and the firing frequency (Hz) (11.55.39) of pyramidal neurons in the The firing frequency of the intermediate neurons (17.36 1.59) was significantly lower than that of the control group (28.49 1.18). The percentage of the energy in the 0.7 12 Hz frequency band (54.65 3.17) of the experimental group was significantly lower than that of the control group (73.29 1.32). The frequency of the experimental group was 12 35 Hz. The percentage of segment energy in total energy (28.85 65 (49.15 + 2.40) decreased significantly, and the percentage of energy to total energy in 12-35 Hz band (24.44 + 1.63) was significantly higher than that in control group (19.47 + 0.82). There was no significant change in the percentage of energy in other bands. The correlation coefficient of the experimental group was significantly higher than that of the control group in the frequency band of 0.7-12 Hz (0.52+0.02) and in the frequency band of 12-35 Hz (0.49+0.02) than that of the control group (0.40+0.01). The mean phase congruence (0.51 65 There is an important fiber projection between the brain regions, which provides a theoretical basis for the treatment of Parkinson's disease.
【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】：2016
【分類號(hào)】：R742.5
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本文編號(hào)：2230391