神经元房室模型与基底核回路分析
发布时间：2018-11-10 15:07
【摘要】：计算神经科学,也称为理论神经科学,是从神经系统结构的信息处理特性角度来研究脑功能,其重点研究真实神经元和神经系统的生物物理模型以及它们的生理学和动力学行为.因此,构建可以抓住生物系统本质特征的回路模型对理解神经系统的功能起着关键作用.本论文主要研究与基底核相关的神经元和神经回路,对多巴胺神经元的单房室模型、中等多棘神经元的多房室模型和皮层-基底核-丘脑回路进行了动力学分析和仿真模拟.本论文的主要工作如下:第一章主要介绍Hodgkin-Huxley模型与Rall电缆模型的理论基础,并给出树突的生物物理机制.Hodgkin-Huxley模型是基于大量实验提出的,利用数学方法刻画神经元的动作电位如何发起和传播的经典模型.Rall模型是描述树突树内的电流是如何传播的经典范例.首先给出这两个模型的详细推导过程,然后简单介绍了房室模型和树突检测机制,最后提出本文研究的主要内容.第二章研究高维神经元模型的降维及其降维后模型的动力学性质.首先利用变量的相关性对原始的十三维模型分两步进行降维并得到一个三维简化系统.然后通过同时改变两个参数来讨论单个簇内锋数目的变化规律.最后分析三维系统的余维2分支,并给出Bogdanov-Takens分支附近的分支行为.第三章研究中等多棘神经元的多房室模型,主要分析外源因素与内源因素对中等多棘神经元放电节律的影响.首先建立基于生物解剖的中等多棘神经元多房室模型,通过对比中等多棘神经元对直流、交流和方波三种电流刺激模式的响应,得到丰富的发放模式,特别研究了外界交流刺激的变化对中等多棘神经元放电节律的影响.其次,通过改变不同离子(钠、钾和钙)通道的最大电导系数或通透性来分析其对中等多棘神经元活动特性的影响.最后,通过移除部分树突的方法模拟部分树突死亡与退化对中等多棘神经元的影响,在相同的外界刺激条件下,通过对比得出五种缺失情况与完整神经元胞体放电的差异.研究结果表明,所有的内源与外源因素对于中等多棘神经元的放电节律均有重要影响,且首次模拟分析树突结构对胞体放电的检测作用.第四章研究皮层-基底核-丘脑回路的动力学机制.第一部分简单介绍基底核的构造、回路连接以及脑深部电刺激.第二部分模拟高频电刺激不同的靶点治疗帕金森病.首先根据生物解剖结构,利用基于电导的神经元模型构建了一个皮层-基底核-丘脑回路模型.以三个不同的核区为靶点,模拟并分析在不同的刺激持续时间和周期下三个靶点的刺激疗效的多样性.然后,采用不同的刺激强度作用于这三个靶点,对比分析不同的刺激强度和靶点对帕金森病治疗的影响.为了确定最优靶点,对两个主要通路对丘脑的不同的影响进行计算.结果表明,构建的皮层-基底核-丘脑回路模型是可靠的,并通过该模型证明高频刺激这三个靶点可以改善丘脑的病理节律.同时还证明了直接通路兴奋丘脑,间接通路对丘脑起着调节作用.第三部分主要研究皮层-基底核-丘脑回路中的信号传导机制.基于相同的理论基础构建另一个皮层-基底核-丘脑回路模型并得到回路中各神经元的不同的放电模式.考虑不同的内因和外因作用下对回路中下游神经元的影响.首先通过改变兴奋性突触连接强度得到下游的底丘脑核与苍白球外侧部神经元之间彼此相互促进和抑制,以及丘脑神经元的放电特性.其次改变抑制性突触连接强度得到下游神经元之间信号传导的相关性.然后探讨不同外界刺激作用于底丘脑核时回路中下游神经元的放电特性.作为对比,最后讨论超极化电流刺激苍白球内侧部,传出神经元的放电特性。
[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.
【学位授予单位】：华南理工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R338
[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.
【学位授予单位】：华南理工大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R338
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