Mechanisms by which cell geometry controls repetitive impulse firing in retinal ganglion cells
Mechanisms by which cell geometry controls repetitive impulse firing in retinal ganglion cells
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DOI：
10.1152/jn.1997.78.4.1948
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发表时间：
1997-10-01
影响因子：
2.5
通讯作者：
Miller, RF
中科院分区：
文献类型：
--
作者：
Fohlmeister, JF;Miller, RF
基于两栖动物视网膜神经节细胞形态的多室表征，开发了产生重复脉冲活动的模型。每个模型包括五个非线性离子通道和一个线性（泄漏）通道。设计离子通道类型和密度的房室分布以模拟在完整视网膜-眼杯制备物中进行的全细胞记录实验。模型和生理学之间的对应关系强调了脉冲波形中通道特定的细节，基于相位图分析、频率与电流（F/I）特性和注入索马的电流的峰间轨迹，以及在顺向和逆向方向上进行脉冲的能力。两种一般类型的模型，包括等效的圆柱表示和更现实的划分的树枝状形态。这些多房室模型包括树突树、索马、轴突丘、薄轴突段和薄段远端轴突的表示。采用代表单个神经元的大量隔室（小于或等于800）以确保在膜电位的最陡变化速率期间相邻隔室之间的最大电压差是可接受的小。漏电导从3到8 μ S/cm（2）不等。结果建立，间室电流，由于不均匀的形态，占主导地位的interspike间隔的膜电流，从而发挥了重要作用，在确定脉冲间距和脉冲序列所携带的信息。输入电阻的变化远不如离子通道存在于树突状隔室中用于调节F/I特性的程度重要。细胞的几何形状，包括薄轴突的地方显着的限制所需的离子通道的位置，以支持冲动的启动和传播的正交和逆向方向。冲动起始的部位变化很大，取决于刺激的大小。符合生理约束的模型也显示出不规则的放电，特别是对于索马的近阈值刺激，这是由于多个冲动起始位点。这种行为可以代表细胞在低对比度刺激条件下传达信息的资产。多个锋电位起始区还可以根据细胞活化的水平为视网膜神经节细胞提供多种反应特征，包括锋电位双峰。增加树枝状等效圆柱体的直径降低了脉冲频率（F/I）响应。在一个有限的范围内的离子通道密度的树突树，树突细胞膜振荡和体细胞尖峰之间的相位锁定可以发生与树突刺激，和数学的混乱，可以证明当足够薄的树突状过程。我们的结论是，细胞形态是在确定发射模式和脉冲频率响应的一个给定的细胞的主要因素，在整个人口的细胞通道密度分布的差异发挥，最多，在这个功能中的次要作用。这一结论适用于索马的突触激活和电极刺激。
Models for generating repetitive impulse activity were developed based on multicompartmental representations of ganglion cell morphology in the amphibian retina. Each model includes five nonlinear ion channels and one linear (leakage) channel. Compartmental distribution of ion channel type and density was designed to simulate whole cell recording experiments carried out in the intact retina-eyecup preparation. Correspondence between the model and physiology emphasized channel-specific details in the impulse waveform, based on phase plot analysis, frequency versus current (F/I) properties, and interspike trajectories for current injected into the soma, as well as the ability to conduct impulses in both orthodromic and antidromic directions. Two general types of model are developed, including equivalent cylinder representations and more realistic compartmentalizations of dendritic morphology. These multicompartmental models include representations for dendritic trees, soma, axon hillock, a thin axonal segment, and axon distal to thin segment. A large number of compartments (less than or equal to 800) representing a single neuron were employed to ensure that maximum voltage differences between neighboring compartments during the steepest rates of change of membrane potential were acceptably small. Leakage conductance varied from 3 to 8 mu S/cm(2). The results establish that intercompartmental currents, due to inhomogeneous morphology, dominate membrane currents in the interspike intervals and thus play a major role in determining the impulse spacing and the information carried by impulse trains. Variations in input resistance are far less important than the degree to which ion channels are present in the dendritic compartments for the regulation of F/I properties. Cell geometry, including the thin axonal places significant constraints on the location of ion channels required to support impulse initiation and propagation in both the ortho-and antidromic directions. The site of impulse initiation varies greatly and depends on the stimulus magnitude. Mod els that conform to physiological constraints also show irregular firing, particularly for near threshold stimulation of the soma, due to multiple sites of impulse initiation. Such behavior could represent an asset to the cells for conveying information under conditions of low contrast stimulation. Multiple spike initiation zones also can provide retinal ganglion cells with a variety of response characteristics, including spike doublets, depending on the level of cell activation. Increasing the diameter of the dendritic equivalent cylinder reduces the impulse frequency (F/I) response. Over a restricted range of ion channel densities in the dendritic tree, phase locking between dendritic membrane oscillations and somatic spiking can occur with dendritic stimulation, and mathematical chaos can be demonstrated when sufficiently thin dendritic processes are present. We conclude that cell morphology is the primary factor in determining firing patterns and the impulse frequency response of a given cell and that differences in channel density distribution across a population of cells plays, at most, a secondary role in this function. This conclusion applies to both synaptic activation and electrode stimulation of the soma.