内嗅皮层对海马癫痫样放电影响的计算模型研究

发布时间：2018-05-18 23:16

本文选题：计算模型 + 海马CA3区　；参考：《上海交通大学》2014年硕士论文

【摘要】：颞叶癫痫是成人癫痫最常见的一种，大部分的颞叶癫痫患者被认为患有难治性癫痫。内嗅皮层（entorhinal cortex，EC）和海马都是边缘系统的重要组成部分，对颞叶癫痫的产生有重要的作用。动物实验研究发现用无镁人工脑脊液（artificialcerebrospinal fluid，ACSF）灌流海马脑片，海马产生间歇期样放电，用无镁ACSF灌流EC-海马联合脑片，海马产生间歇期样和发作样放电交互出现的癫痫样放电，我们猜测海马发作样放电的产生与EC有紧密的关系。丙戊酸（valproate，VPA）是一种常用的抗癫痫药物，，动物实验研究发现，VPA不能阻断EC-海马联合脑片上的间歇期样放电，但能阻断EC-海马联合脑片上的发作样放电。目前对这一实验现象的机制还不是很清楚。本论文通过建立海马CA3区网络模型，对上述实验现象进行模拟并探索可能的机制。本论文的工作主要包括三个部分：（1）建立海马CA3区网络模型，包括两个锥体细胞，一个篮状细胞和一个始层分子层细胞，根据解剖学证据构建神经元之间的连接以及网络中受体通道的分布等。（2）在没有EC输入的网络模型中，改变镁离子浓度，模拟无镁ACSF灌流海马脑片产生间歇期样放电的实验现象。给网络加入EC的信号输入，模拟无镁ACSF灌流EC-海马联合脑片产生间歇期样和发作样放电交互出现的实验现象。（3）增强网络中GABA能的抑制性连接强度和降低网络中NMDA能的兴奋性连接强度，模拟VPA对海马网络的作用。研究结果表明，改变网络中的镁离子浓度至0mM，海马CA3区能产生间歇期样放电，并且给网络加入含有发作样放电的EC信号输入，网络能产生发作样放电。研究结果证明在EC-海马联合脑片上，海马区发作样放电的产生可能是由EC引起的。在没有EC输入的网络模型中，增强网络中GABA能的抑制性连接强度和降低NMDA能的兴奋性连接强度，可以降低网络中间歇期样放电的频率，模拟VPA对海马间歇期样放电的影响。在有EC信号输入的网络模型中，当EC只含有间歇期样放电时，网络产生间歇期样放电，增强网络中GABA能的抑制性连接强度和降低NMDA能的兴奋性连接强度，网络中间歇期样放电仍然存在；当EC含有间歇期样和发作样放电时，网络产生间歇期样和发作样放电，增强网络中GABA能的抑制性连接强度和降低NMDA能的兴奋性连接强度，不能将网络中的发作样放电阻断。网络中发作样放电的消失可能是EC输入信号不包含发作样放电导致的。因此，我们推测VPA能够阻断EC-海马联合脑片上的发作样放电可能是由于VPA阻断了EC的发作样放电，导致海马区的发作样放电消失。本论文的研究意义在于从计算模型的角度研究EC对海马癫痫样放电的影响。通过调节EC对模型的输入信号，模拟动物实验现象，推测实验现象存在的可能机制。本文建立的CA3区网络模型具有较强的通用性，在今后的研究工作中，该计算模型也能用于研究其他有关癫痫样放电的实验现象。
[Abstract]:Temporal lobe epilepsy is the most common type of adult epilepsy, most of the temporal lobe epilepsy patients are considered to have intractable epilepsy. The entorhinal cortex (EC) and the hippocampus are important parts of the marginal system, which have an important role in the generation of temporal lobe epilepsy. Animal experimental studies found that the magnesium free cerebrospinal fluid (artificialcerebro) is used in the animal experiment. Spinal fluid, ACSF) perfusion of hippocampal slices, hippocampus produces intermittent phase like discharge, using magnesium free ACSF perfusion EC- hippocampus combined brain slices, hippocampus produces intermittent phase like and seizure like discharge interactively epileptic discharge, we guess that the formation of hippocampal epileptic discharge is closely related to EC. Valproic acid (valproate, VPA) is a common antiepileptic. Drug, animal experiments have found that VPA can not block the intermittent phase like discharge on the EC- hippocampus combined with brain slices, but can block the seizure like discharge on the EC- hippocampus combined with the brain slices. The mechanism of this experimental phenomenon is not very clear at present. This paper simulates and explores the above experimental phenomena by establishing a network model of the hippocampus CA3 region. The mechanism.
The work of this thesis mainly consists of three parts: (1) the establishment of a CA3 network model in the hippocampus, including two pyramidal cells, a basket like cell and a layer of molecular layer cells in the beginning, constructing the connections between neurons according to the anatomical evidence and the distribution of the receptor channel in the network. (2) change magnesium ions in a network model without EC input. Concentration, simulation of the experimental phenomenon of intermittent period like discharge in hippocampal slices of magnesium free ACSF perfusion. Input the EC signal to the network, simulate the experimental phenomena of intermission like and epileptiform discharges produced by EC- hippocampus combined brain slices without magnesium ACSF perfusion. (3) enhance the inhibitory connection strength of GABA energy in the network and reduce the NMDA energy in the network. The intensity of excitatory connectivity simulated the effect of VPA on hippocampal network.
The results show that changing the concentration of magnesium ions in the network to 0mM, the hippocampal CA3 region can produce batch discharge, and the network can produce EC signal input containing the attack like discharge, and the network can produce a seizure like discharge. The results show that the occurrence of epileptic discharge in the hippocampus may be caused by EC on the EC- hippocampal joint brain slices. In the network model with EC input, the enhancement of the inhibitory connection strength of GABA energy in the network and the decrease of the excitatory connection intensity of the NMDA energy can reduce the frequency of the intermittent phase discharge in the network and simulate the effect of VPA on the batch discharge of the hippocampus. In the network model with EC signal input, when EC only contains batch discharge, the network produces Intermittent phase discharge, which increases the inhibitory connection strength of GABA energy in the network and reduces the excitatory connection intensity of NMDA energy, still exists in the Internet interphase discharge in the network. When EC contains batch and episode like discharge, the network produces intermittent and episode like discharge, enhancing the inhibitory connection strength of GABA energy in the network and reducing the NMDA energy. The excitability connection strength can not block the attack like discharge in the network. The disappearance of the attack like discharge in the network may be that the EC input signal does not contain a seizure like discharge. Therefore, we speculate that VPA can block the seizure like discharge on the EC- hippocampal joint brain slices, which may be due to the interruption of EC's seizure like discharge by VPA, leading to the hippocampus The seizure like discharge disappeared.
The research significance of this thesis is to study the effect of EC on epileptic discharge in the hippocampus from the point of view of the computational model. By adjusting the input signals of the EC model and simulating the animal experiment phenomena, we can speculate the possible mechanism of the existence of the experimental phenomena. The CA3 network model established in this paper has strong usage, and the computational model is in the future research work. It can also be used to study other experimental phenomena related to epileptiform discharges.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1

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