丙泊酚麻醉抑制工作记忆LFPs网络和神经元群体电活动的研究

发布时间：2018-04-25 17:36

本文选题：工作记忆 + 局部场电位　；参考：《天津医科大学》2014年硕士论文

【摘要】：研究目的：丙泊酚是临床常用静脉麻醉药,丙泊酚麻醉对大脑认知功能的影响是麻醉临床关注的热点。工作记忆是一类重要的认知功能,前额叶皮层是工作记忆的关键脑区之一。本论文基于在体植入式微电极记录的两类不同模态神经信号：局部场电位(Local field potential, LFP)和动作电位(Action potential, AP),分析LFPs功能连接网络特性和和神经元群体的电活动,研究丙泊酚麻醉对工作记忆的抑制机制,为临床丙泊酚麻醉提供理论支持。研究方法： 1.实验动物为8-10周龄雄性SD大鼠14只,体重300-350g; 2.大鼠进行Y迷宫工作记忆任务训练,直到连续三天平均正确率达到85%; 3.丙泊酚麻醉大鼠模型的制备：大鼠随机分为两组,丙泊酚组(n=7,麻醉剂量为0.9mg/kg·min尾静脉注射丙泊酚2h)和对照组(n=7); 4.在大鼠前额叶皮层植入16通道微电极阵列,应用在体植入式微电极阵列记录技术,记录大鼠在Y迷宫工作记忆过程中前额叶皮层多通道神经信号,从中获取两种不同模态神经信号：多通道LFPs和神经元集群的动作电位时空序列； 5.LFPs的时频分析,获取工作记忆的特征频段； 6.研究丙泊酚麻醉对工作记忆LFPs的0频段、γ频段功能连接网络特性的抑制作用； 7.计算工作记忆参考点前2s的神经元群体平均发放频率,将高于平均频率的神经元募集为编码工作记忆事件的神经元集群。研究丙泊酚麻醉对工作记忆神经元群体集群电活动和群体中每个神经元电活动的抑制作用。研究结果： 1.剂量为0.9mg/kg·min,2h的丙泊酚麻醉后24、48、72h对大鼠Y迷宫工作记忆行为学影响的结果：与对照组比较,麻醉后24h丙泊酚组57%±5%,对照组90%±3%(p0.01);麻醉后48h丙泊酚组75%±4%,对照组91%±2%(p0.05)；麻醉后72h:丙泊酚组88%±3%,对照组90%±3%(p0.05)。 2.丙泊酚麻醉后24、48、72h对大鼠工作记忆LFPs特征分量的影响大鼠在工作记忆任务过程中,LFPs能量曲线的峰值发生在工作记忆参考点前2s时间段内,峰值前后各0.5s时段内工作记忆LFPs的0和γ频段的能量明显高于其它时间段(p0.05)。丙泊酚组与对照组结果相比,麻醉后24h:丙泊酚组LFPs的0频段能量峰值下降(p0.05),Y频段能量峰值显著下降(p0.01);麻醉后48h:丙泊酚组LFPs的0频段能量下降(p0.05),γ频段能量下降(p0.05)；麻醉后72h两组大鼠LFPs的0频段和γ频段能量峰值无差异(p0.05)。 3.丙泊酚麻醉后24、48、72h对工作记忆LFPs功能连接的影响麻醉后24h,LFPs的0频段分量DTF值：丙泊酚组为0.0082±0.0021,对照组为0.0162±0.0012(p0.01)；LFPs的γ频段分量DTF值：丙泊酚组为0.0032±0.0011,对照组为0.0122±0.0013(P0.01)。麻醉后48h,LFPs的0频段分量DTF值：丙泊酚组为0.0140±0.0023,对照组为0.0165±0.0019(p0.05)；LFPs的丫频段分量DTF值：丙泊酚组为0.0065±0.0013,对照组为0.0119±0.0028(p0.01)。麻醉后72h,LFPs的0频段分量DTF值：丙泊酚组为0.0157±0.0029,对照组为0.0165±0.0014(p0.05)；LFPs的γ频段分量DTF值：丙泊酚组为0.0117±0.0024,对照组为0.0121±0.0015(p0.05)。 4.丙泊酚麻醉后24、48、72h对工作记忆LFPs网络特性的影响 (1)丙泊酚麻醉对工作记忆LFPs网络连接密度D的影响：麻醉后24h, LFPs的θ频段分量：丙泊酚组为0.22±0.03,对照组为0.42±0.07(p0.01):LFPs的γ频段分量：丙泊酚组为0.12±0.03,对照组为0.63±0.05(p0.01)。麻醉后48h,LFPs的0频段分量：丙泊酚组为0.30±0.04,对照组为0.48±0.06(p0.05);LFPs的γ频段分量：丙泊酚组为0.48±0.04,对照组为0.62±0.03(p0.05)。麻醉后72h,LFPs的0频段分量：丙泊酚组为0.41±0.02,对照组为0.47±0.05(p0.05)；LFPs的γ频段分量：丙泊酚组为0.61±0.05,对照组为0.63±0.04(p0.05)。 (2)丙泊酚麻醉对工作记忆LFPs网络信息传递效率Eglobal的影响：麻醉后24h, LFPs的0频段分量：丙泊酚组为0.57±0.02,对照组为0.62±0.04(p0.05);LFPs的γ频段分量：丙泊酚组为0.24±0.02,对照组为0.72±0.06(p0.01)。麻醉后48h,LFPs的0频段分量：丙泊酚组为0.58±0.04,对照组为0.67±0.02(p0.05)；LFPs的γ频段分量：丙泊酚组为0.49±0.07,对照组为0.73±0.02(p0.05)。麻醉后72h, LFPs的0频段分量：丙泊酚组为0.62±0.02,对照组为0.66±0.02(p0.05)；LFPs的γ频段分量：丙泊酚组为0.69±0.04,对照组为0.73±0.04(p0.05)。 5.丙泊酚麻醉后24、48、72h对工作记忆大鼠神经元群体电活动的影响 (1)丙泊酚麻醉对工作记忆神经元集群频率编码的影响：与对照组结果相比,麻醉后24、48h丙泊酚组编码工作记忆事件的神经元集群个数显著下降(p10.01,p20.05)；麻醉后72h两组无差异(p0.05)。 (2)丙泊酚麻醉对工作记忆神经元群体中每个神经元电活动的影响：与对照组结果相比,编码工作记忆事件的神经元集群中神经元电活动占神经元群体比例在麻醉后24h:丙泊酚组为24.3%±4.7%,对照组为80.6%±13.5%(p0.01)；麻醉后48h:丙泊酚组为48.6%±11.2%,对照组为81.2%±11.4%(p0.05)；麻醉后72h:丙泊酚组为78.3%±10.2%,对照组为82.6%±15.1%(p0.05)。研究结论： 1.剂量为0.9mg/kg·min,2h的丙泊酚麻醉,在48h内对大鼠工作记忆任务的执行存在明显抑制作用,72h后无抑制作用： 2.大鼠LFPs的0(4-12HZ)和γ频段(30-60HZ)分量在编码工作记忆过程起关键作用。剂量为0.9mg/kg·min,2h的丙泊酚麻醉,在48h内对LFPs的γ频段特征分量抑制作用显著,72h后无抑制作用； 3.LFPs的γ频段分量功能连接在丙泊酚麻醉后48h内被显著抑制,72h后无抑制作用；而0频段分量的功能连接仅在丙泊酚麻醉后24小时内被抑制； 4.丙泊酚麻醉后48h内显著抑制LFPs的θ和γ频段网络连接密度,72h后无抑制作用； 5.丙泊酚麻醉后48h内显著抑制LFPs的γ频段分量的网络信息传递效率,72h后无抑制作用,剂量为0.9mg/kg·min,2h的丙泊酚麻醉对θ频段的网络信息传递效率无抑制作用； 6.丙泊酚麻醉后48h内明显抑制神经元集群电活动与群体中每个神经元的电活动,72h后无抑制作用。
[Abstract]:The purpose of the study is:
Propofol is a commonly used intravenous anesthetic. The effect of propofol on cognitive function of the brain is the focus of clinical attention. Working memory is one of the most important cognitive functions. The prefrontal cortex is one of the key brain regions of working memory. This paper is based on two different modal neural signals recorded in body implantable microelectrodes: local The field potential (Local field potential, LFP) and action potential (Action potential, AP) are used to analyze the characteristics of the functional connection network of LFPs and the electrical activity of the neuronal population, and to study the mechanism of the suppression of working memory by propofol anesthesia, and provide theoretical support for the clinical propofol anesthesia.
Research methods:
1. the experimental animals were 14 male SD rats aged 8-10 weeks, weighing 300-350g.
2. rats were trained in Y maze task memory task until the average three day accuracy rate was 85%.
3. the rat model of propofol anesthetized: rats were randomly divided into two groups, propofol group (n=7, anesthetic dose of 0.9mg/kg min caudal intravenous propofol 2H) and control group (n=7).
4. the 16 channel microelectrode arrays were implanted in the prefrontal cortex of the rat, and the multichannel neural signals were recorded in the prefrontal cortex of the Y labyrinth labyrinth of rats, and two different modal neural signals were obtained from the body embedded microelectrode array recording technique, and the action potential spatiotemporal sequence of the multichannel LFPs and the God Jing Yuan cluster was obtained.
5.LFPs's time-frequency analysis is used to get the characteristic frequency of working memory.
6. to study the inhibitory effect of propofol anesthesia on the 0 band and gamma band functional connectivity network of working memory LFPs.
7. the average frequency of neuronal population distribution before the working memory reference point 2S was calculated, and the neurons raised above the average frequency were collected as the neurons of the coded working memory events. The inhibitory effect of propofol anesthesia on the group electrical activity of working memory neurons and the electrical activity of each neuron in the group was investigated.
The results of the study:
1. dose of 0.9mg/kg. Min, the effect of 24,48,72h on the working memory behavior of Y maze after anaesthesia of 2h in rats: compared with the control group, 24h propofol group after anesthesia was 57% + 5%, and the control group was 90% + 3% (P0.01); 48h propofol group was 75% + 4% after anesthesia, and the control group was 91% + 2% (P0.05); 72h: propofol group after anesthesia was 88% + 57%, and the control group 90% + 3% (p0.0) 5).
2. effects of propofol 24,48,72h on LFPs characteristic components of working memory in rats
During the working memory task, the peak of the LFPs energy curve occurred in the 2S period before the working memory reference point. The energy of the 0 and the gamma band of the working memory LFPs in the 0.5s period of the peak before and after the peak was significantly higher than that of the other time periods (P0.05). The 0 frequency band energy peak of the LFPs in the 24h: propofol group after anaesthesia was compared with the control group. The energy peak of Y band decreased significantly (P0.01), the 0 band energy of LFPs in 48h: propofol group decreased (P0.05), and the energy of gamma frequency band decreased (P0.05) after anesthesia, and there was no difference between the 0 band and the gamma band energy peak of 72h two rats after anesthesia (P0.05).
3. the effect of 24,48,72h on functional connectivity of working memory LFPs after propofol anesthesia
The 0 band component DTF value of 24h and LFPs after anesthesia was 0.0082 + 0.0021 in propofol group and 0.0162 + 0.0012 in control group (P0.01), and the DTF value of LFPs was 0.0032 + 0.0011 in propofol group and 0.0122 + 0.0013 (P0.01) in control group. The 0 frequency component DTF value of 48h and LFPs after anesthesia: Propofol group 0.0140 + 0.0023 and control group 0.0165 + 0.001 9 (P0.05); the DTF value of the frequency segment of LFPs: the propofol group was 0.0065 + 0.0013, the control group was 0.0119 + 0.0028 (P0.01). The DTF value of the 0 band components of 72h and LFPs after anesthesia was 0.0157 + 0.0029 in the propofol group and 0.0165 + 0.0014 (P0.05) in the control group; the DTF value of the gamma frequency component of LFPs: Propofol group was 0.0117 + 0.0024, and the control group was 0.0121 + 0.001 5 (P0.05).
4. effects of propofol anesthesia on 24,48,72h working memory LFPs network characteristics
(1) the effect of propofol anesthesia on the D density of working memory LFPs network:
After anaesthesia, 24h, LFPs was 0.22 + 0.03, and the control group was 0.42 + 0.07 (P0.01): the gamma frequency component of LFPs was 0.12 + 0.03 in the propofol group and 0.63 + 0.05 (P0.01) in the control group. The 0 band components of 48h and LFPs after anesthesia were 0.30 + 0.04, and the control group was 0.48 + 0.06 (P0.05); and the gamma frequency component of LFPs: propofol. The group was 0.48 + 0.04 and the control group was 0.62 + 0.03 (P0.05). The 0 band components of 72h and LFPs after anesthesia were 0.41 + 0.02 in propofol group and 0.47 + 0.05 (P0.05) in the control group; the gamma frequency component of LFPs was 0.61 + 0.05 in propofol group and 0.63 + 0.04 in the control group (P0.05).
(2) the effect of propofol anesthesia on the information transmission efficiency Eglobal of working memory LFPs network:
The 0 band components of 24h and LFPs after anesthesia were 0.57 + 0.02 in propofol group and 0.62 + 0.04 (P0.05) in the control group; the gamma frequency component of LFPs was 0.24 + 0.02 in propofol group and 0.72 + 0.06 (P0.01) in the control group. The 0 band components of 48h and LFPs after anesthesia: Propofol group was 0.58 + 0.04, and the control group was 0.67 + P0.05; and LFPs's gamma frequency component: propos The phenol group was 0.49 + 0.07 and the control group was 0.73 + 0.02 (P0.05). The 0 band components of 72h and LFPs after anesthesia were 0.62 + 0.02 in propofol group and 0.66 + 0.02 (P0.05) in the control group. The gamma frequency component of LFPs was 0.69 + 0.04 in propofol group and 0.73 + 0.04 in the control group (P0.05).
5. effects of propofol anesthesia on the electrical activity of neurons in working memory rats after 24,48,72h
(1) the effect of propofol anesthesia on the frequency coding of working memory neurons.
Compared with the control group, the number of neuron clusters in the 24,48h propofol group coded working memory events after anesthesia was significantly decreased (p10.01, p20.05), and there was no difference in the 72h two groups after anesthesia (P0.05).
(2) the effect of propofol anesthesia on the electrical activity of each neuron in the working memory neuron population.
Compared with the control group, the proportion of neuron electrical activity in the neuron group in the neurons of the coded working memory event was 24.3% + 4.7% in the 24h: propofol group after anesthesia and 80.6% + 13.5% (P0.01) in the control group, 48.6% + 11.2% in the 48h: propofol group after anesthesia and 81.2% + (P0.05) in the control group, and 78.3% + in the 72h: propofol group after anesthesia. 10.2%, the control group was 82.6% + 15.1% (P0.05).
The conclusions are as follows:
1. doses of 0.9mg/kg? Min, 2h propofol anesthesia, 48h in the implementation of working memory tasks in rats significantly inhibited, after 72h no inhibition effect:
The 0 (4-12HZ) and gamma band (30-60HZ) components of LFPs in 2. rats play a key role in coding working memory process. The dose of 0.9mg/kg. Min, 2h in propofol anesthesia, in 48h has significant inhibitory effect on the characteristic component of LFPs frequency band, and there is no inhibition after 72h.
The functional connection of 3.LFPs's gamma band components was significantly inhibited in 48h after propofol anesthesia and no inhibition after 72h, while the functional connection of the 0 band components was inhibited only within 24 hours after propofol anesthesia.
4. after anesthesia with propofol, 48h significantly inhibited the network density of LFPs theta and gamma band, and had no inhibitory effect after 72h.
After 5. propofol anaesthesia, 48h significantly inhibited the network information transmission efficiency of the gamma frequency component of LFPs, no inhibition after 72h, the dose of 0.9mg/kg. Min, and 2H's propofol anesthesia had no inhibitory effect on the network information transmission efficiency of the theta frequency band.
6. after propofol anesthesia, 48h significantly inhibited the electrical activity of neurons and the electrical activity of each neuron in the population, but 72h had no inhibitory effect.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R614

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