【摘要】：計(jì)算神經(jīng)科學(xué),也稱為理論神經(jīng)科學(xué),是從神經(jīng)系統(tǒng)結(jié)構(gòu)的信息處理特性角度來(lái)研究腦功能,其重點(diǎn)研究真實(shí)神經(jīng)元和神經(jīng)系統(tǒng)的生物物理模型以及它們的生理學(xué)和動(dòng)力學(xué)行為.因此,構(gòu)建可以抓住生物系統(tǒng)本質(zhì)特征的回路模型對(duì)理解神經(jīng)系統(tǒng)的功能起著關(guān)鍵作用.本論文主要研究與基底核相關(guān)的神經(jīng)元和神經(jīng)回路,對(duì)多巴胺神經(jīng)元的單房室模型、中等多棘神經(jīng)元的多房室模型和皮層-基底核-丘腦回路進(jìn)行了動(dòng)力學(xué)分析和仿真模擬.本論文的主要工作如下:第一章主要介紹Hodgkin-Huxley模型與Rall電纜模型的理論基礎(chǔ),并給出樹(shù)突的生物物理機(jī)制.Hodgkin-Huxley模型是基于大量實(shí)驗(yàn)提出的,利用數(shù)學(xué)方法刻畫(huà)神經(jīng)元的動(dòng)作電位如何發(fā)起和傳播的經(jīng)典模型.Rall模型是描述樹(shù)突樹(shù)內(nèi)的電流是如何傳播的經(jīng)典范例.首先給出這兩個(gè)模型的詳細(xì)推導(dǎo)過(guò)程,然后簡(jiǎn)單介紹了房室模型和樹(shù)突檢測(cè)機(jī)制,最后提出本文研究的主要內(nèi)容.第二章研究高維神經(jīng)元模型的降維及其降維后模型的動(dòng)力學(xué)性質(zhì).首先利用變量的相關(guān)性對(duì)原始的十三維模型分兩步進(jìn)行降維并得到一個(gè)三維簡(jiǎn)化系統(tǒng).然后通過(guò)同時(shí)改變兩個(gè)參數(shù)來(lái)討論單個(gè)簇內(nèi)鋒數(shù)目的變化規(guī)律.最后分析三維系統(tǒng)的余維2分支,并給出Bogdanov-Takens分支附近的分支行為.第三章研究中等多棘神經(jīng)元的多房室模型,主要分析外源因素與內(nèi)源因素對(duì)中等多棘神經(jīng)元放電節(jié)律的影響.首先建立基于生物解剖的中等多棘神經(jīng)元多房室模型,通過(guò)對(duì)比中等多棘神經(jīng)元對(duì)直流、交流和方波三種電流刺激模式的響應(yīng),得到豐富的發(fā)放模式,特別研究了外界交流刺激的變化對(duì)中等多棘神經(jīng)元放電節(jié)律的影響.其次,通過(guò)改變不同離子(鈉、鉀和鈣)通道的最大電導(dǎo)系數(shù)或通透性來(lái)分析其對(duì)中等多棘神經(jīng)元活動(dòng)特性的影響.最后,通過(guò)移除部分樹(shù)突的方法模擬部分樹(shù)突死亡與退化對(duì)中等多棘神經(jīng)元的影響,在相同的外界刺激條件下,通過(guò)對(duì)比得出五種缺失情況與完整神經(jīng)元胞體放電的差異.研究結(jié)果表明,所有的內(nèi)源與外源因素對(duì)于中等多棘神經(jīng)元的放電節(jié)律均有重要影響,且首次模擬分析樹(shù)突結(jié)構(gòu)對(duì)胞體放電的檢測(cè)作用.第四章研究皮層-基底核-丘腦回路的動(dòng)力學(xué)機(jī)制.第一部分簡(jiǎn)單介紹基底核的構(gòu)造、回路連接以及腦深部電刺激.第二部分模擬高頻電刺激不同的靶點(diǎn)治療帕金森病.首先根據(jù)生物解剖結(jié)構(gòu),利用基于電導(dǎo)的神經(jīng)元模型構(gòu)建了一個(gè)皮層-基底核-丘腦回路模型.以三個(gè)不同的核區(qū)為靶點(diǎn),模擬并分析在不同的刺激持續(xù)時(shí)間和周期下三個(gè)靶點(diǎn)的刺激療效的多樣性.然后,采用不同的刺激強(qiáng)度作用于這三個(gè)靶點(diǎn),對(duì)比分析不同的刺激強(qiáng)度和靶點(diǎn)對(duì)帕金森病治療的影響.為了確定最優(yōu)靶點(diǎn),對(duì)兩個(gè)主要通路對(duì)丘腦的不同的影響進(jìn)行計(jì)算.結(jié)果表明,構(gòu)建的皮層-基底核-丘腦回路模型是可靠的,并通過(guò)該模型證明高頻刺激這三個(gè)靶點(diǎn)可以改善丘腦的病理節(jié)律.同時(shí)還證明了直接通路興奮丘腦,間接通路對(duì)丘腦起著調(diào)節(jié)作用.第三部分主要研究皮層-基底核-丘腦回路中的信號(hào)傳導(dǎo)機(jī)制.基于相同的理論基礎(chǔ)構(gòu)建另一個(gè)皮層-基底核-丘腦回路模型并得到回路中各神經(jīng)元的不同的放電模式.考慮不同的內(nèi)因和外因作用下對(duì)回路中下游神經(jīng)元的影響.首先通過(guò)改變興奮性突觸連接強(qiáng)度得到下游的底丘腦核與蒼白球外側(cè)部神經(jīng)元之間彼此相互促進(jìn)和抑制,以及丘腦神經(jīng)元的放電特性.其次改變抑制性突觸連接強(qiáng)度得到下游神經(jīng)元之間信號(hào)傳導(dǎo)的相關(guān)性.然后探討不同外界刺激作用于底丘腦核時(shí)回路中下游神經(jīng)元的放電特性.作為對(duì)比,最后討論超極化電流刺激蒼白球內(nèi)側(cè)部,傳出神經(jīng)元的放電特性。
[Abstract]:Computational neuroscience, also known as the theory neuroscience, is a study of the brain function from the point of view of the information processing of the nervous system structure, which focuses on the biophysical models of real and nervous systems and their physiological and dynamic behavior. Therefore, the loop model that can grasp the essential characteristics of the biological system plays a key role in understanding the function of the nervous system. The paper mainly deals with the neuronal and neural circuits associated with the basal nucleus, the single-compartment model of the dopaminergic neurons, the multi-compartmental model of the middle-spiny neurons and the cortical-basal-thalamic loop, and the simulation of the simulation is carried out. The main work of this thesis is as follows: The first chapter mainly introduces the theoretical basis of the Hodgkin-Huxley model and the Rall cable model, and gives the biophysics mechanism of the dendrites. The Hodgkin-Huxley model is based on a large number of experiments, using mathematical methods to describe how the action potential of a neuron is initiated and propagated. The Rall model is a classic example of how current in a dendritic tree propagates. First, the detailed derivation of these two models is given, then the AV model and the dendritic detection mechanism are briefly introduced, and the main contents of this study are put forward. In the second chapter, we study the descending dimension of high-dimensional neuron model and the dynamic properties of the reduced-dimension model. First, the original three-dimensional model is divided into two steps by using the correlation of the variable, and a three-dimensional simplified system is obtained. and then the variation law of the number of front points in a single cluster is discussed by changing the two parameters at the same time. Finally, the sub-dimension 2 branch of the three-dimensional system is analyzed, and the branch behavior near the Bogdanov-Takens branch is given. In the third chapter, we study the multi-compartmental model of the middle-multi-spiny neurons, and mainly analyze the effect of the exogenous factors and the endogenous factors on the discharge rhythm of the middle-order spiny neurons. Firstly, a multi-compartmental model based on the biological anatomy is established, and the response of the three current stimulation modes of the direct current, the alternating current and the square wave is compared by the comparison of the middle-multi-spine neuron, so that a rich distribution mode is obtained, In this paper, the effect of the change of external AC stimulation on the discharge rhythm of the middle-order spiny neurons was studied. Secondly, by changing the maximum conductance or permeability of different ions (sodium, potassium, and calcium), the effect of its activity on the activity of the medium-order spiny neurons was analyzed. Finally, by removing some of the dendritic cells, the effects of partial dendritic death and degeneracy on the middle-order spinal neurons were simulated, and the difference of five missing cases and complete neuronal cell discharge was obtained under the same external stimulation conditions. The results show that all the endogenous and exogenous factors have an important effect on the discharge rhythm of the middle and multi-spiny neurons, and the first simulation and analysis of the effect of the dendritic structure on the cell discharge. The fourth chapter studies the dynamic mechanism of the subcortical-basal-thalamic loop. The first part briefly introduces the structure, loop connection and deep brain electrical stimulation of the base core. the second part is used for simulating the high-frequency electrical stimulation to different target points for treating the parkinson's disease. First, according to the biological anatomy, a cortical-basal-thalamic-loop model was constructed using a conductance-based neuronal model. Three different nuclear areas were used as targets to simulate and analyze the diversity of the stimulation efficacy of three targets at different stimulation duration and cycle. The effects of different stimulation intensity and target on the treatment of Parkinson's disease were compared. In order to determine the optimal target, the different effects of the two main pathways on the thalamus were calculated. The results showed that the constructed cortical-basal-thalamic loop model was reliable and demonstrated that the three targets of high frequency stimulation could improve the pathological rhythm of the thalamus by the model. It also proved that the direct pathway is excited to the thalamus, and the indirect pathway plays an important role in the thalamus. The third part mainly studies the signal transduction mechanism in the subcortical-basal-thalamic loop. another cortical-basal-thalamic loop model was constructed on the basis of the same theoretical basis and a different discharge pattern of each neuron in the loop was obtained. The effects of different internal and external factors on the middle and lower reaches of the loop are considered. first of all, by changing the intensity of the excitatory synapse connection, the mutual promotion and inhibition of the subthalamic nucleus and the neurons in the outer part of the pallidus and the discharge characteristics of the thalamus neurons are obtained. Secondly, the correlation of signal conduction between the downstream neurons was obtained by changing the inhibitory synaptic connection strength. The discharge characteristics of the neurons in the middle and lower reaches of the subthalamic nucleus were then discussed. in contrast, that hyperpolarized current stimulate the inner part of the globus pallidus, and the discharge characteristic of the nerve element is transmitted.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R338

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