本文選題：計算模型 + 海馬CA3區(qū)��； 參考：《上海交通大學》2014年碩士論文

【摘要】：顳葉癲癇是成人癲癇最常見的一種，大部分的顳葉癲癇患者被認為患有難治性癲癇。內(nèi)嗅皮層（entorhinal cortex，EC）和海馬都是邊緣系統(tǒng)的重要組成部分，對顳葉癲癇的產(chǎn)生有重要的作用。動物實驗研究發(fā)現(xiàn)用無鎂人工腦脊液（artificialcerebrospinal fluid，ACSF）灌流海馬腦片，海馬產(chǎn)生間歇期樣放電，用無鎂ACSF灌流EC-海馬聯(lián)合腦片，海馬產(chǎn)生間歇期樣和發(fā)作樣放電交互出現(xiàn)的癲癇樣放電，我們猜測海馬發(fā)作樣放電的產(chǎn)生與EC有緊密的關系。丙戊酸（valproate，VPA）是一種常用的抗癲癇藥物，，動物實驗研究發(fā)現(xiàn)，VPA不能阻斷EC-海馬聯(lián)合腦片上的間歇期樣放電，但能阻斷EC-海馬聯(lián)合腦片上的發(fā)作樣放電。目前對這一實驗現(xiàn)象的機制還不是很清楚。本論文通過建立海馬CA3區(qū)網(wǎng)絡模型，對上述實驗現(xiàn)象進行模擬并探索可能的機制。 本論文的工作主要包括三個部分：（1）建立海馬CA3區(qū)網(wǎng)絡模型，包括兩個錐體細胞，一個籃狀細胞和一個始層分子層細胞，根據(jù)解剖學證據(jù)構(gòu)建神經(jīng)元之間的連接以及網(wǎng)絡中受體通道的分布等。（2）在沒有EC輸入的網(wǎng)絡模型中，改變鎂離子濃度，模擬無鎂ACSF灌流海馬腦片產(chǎn)生間歇期樣放電的實驗現(xiàn)象。給網(wǎng)絡加入EC的信號輸入，模擬無鎂ACSF灌流EC-海馬聯(lián)合腦片產(chǎn)生間歇期樣和發(fā)作樣放電交互出現(xiàn)的實驗現(xiàn)象。（3）增強網(wǎng)絡中GABA能的抑制性連接強度和降低網(wǎng)絡中NMDA能的興奮性連接強度，模擬VPA對海馬網(wǎng)絡的作用。 研究結(jié)果表明，改變網(wǎng)絡中的鎂離子濃度至0mM，海馬CA3區(qū)能產(chǎn)生間歇期樣放電，并且給網(wǎng)絡加入含有發(fā)作樣放電的EC信號輸入，網(wǎng)絡能產(chǎn)生發(fā)作樣放電。研究結(jié)果證明在EC-海馬聯(lián)合腦片上，海馬區(qū)發(fā)作樣放電的產(chǎn)生可能是由EC引起的。在沒有EC輸入的網(wǎng)絡模型中，增強網(wǎng)絡中GABA能的抑制性連接強度和降低NMDA能的興奮性連接強度，可以降低網(wǎng)絡中間歇期樣放電的頻率，模擬VPA對海馬間歇期樣放電的影響。在有EC信號輸入的網(wǎng)絡模型中，當EC只含有間歇期樣放電時，網(wǎng)絡產(chǎn)生間歇期樣放電，增強網(wǎng)絡中GABA能的抑制性連接強度和降低NMDA能的興奮性連接強度，網(wǎng)絡中間歇期樣放電仍然存在；當EC含有間歇期樣和發(fā)作樣放電時，網(wǎng)絡產(chǎn)生間歇期樣和發(fā)作樣放電，增強網(wǎng)絡中GABA能的抑制性連接強度和降低NMDA能的興奮性連接強度，不能將網(wǎng)絡中的發(fā)作樣放電阻斷。網(wǎng)絡中發(fā)作樣放電的消失可能是EC輸入信號不包含發(fā)作樣放電導致的。因此，我們推測VPA能夠阻斷EC-海馬聯(lián)合腦片上的發(fā)作樣放電可能是由于VPA阻斷了EC的發(fā)作樣放電，導致海馬區(qū)的發(fā)作樣放電消失。 本論文的研究意義在于從計算模型的角度研究EC對海馬癲癇樣放電的影響。通過調(diào)節(jié)EC對模型的輸入信號，模擬動物實驗現(xiàn)象，推測實驗現(xiàn)象存在的可能機制。本文建立的CA3區(qū)網(wǎng)絡模型具有較強的通用性，在今后的研究工作中，該計算模型也能用于研究其他有關癲癇樣放電的實驗現(xiàn)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.
【學位授予單位】：上海交通大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R742.1

【參考文獻】

相關期刊論文 前3條

1 宮新偉;楊帆;劉建盛;陸欽池;龔海慶;梁培基;張溥明;;應用多電極記錄技術(shù)研究海馬切片癲癇樣放電的起始點和傳播方向[J];生物化學與生物物理進展;2010年11期

2 李靜波;陸欽池;宮新偉;龔海慶;張溥明;梁培基;;外源性鋅離子對大鼠海馬切片癲癇樣放電的起源、傳播與頻率特性的調(diào)節(jié)作用[J];生物物理學報;2012年02期

3 ;Microelectrode array recordings of excitability of low Mg~(2+)-induced acute hippocampal slices[J];Neural Regeneration Research;2010年20期

本文編號：1907644