COMPUTER-SIMULATIONS OF MORPHOLOGICALLY RECONSTRUCTED CA3 HIPPOCAMPAL-NEURONS
COMPUTER-SIMULATIONS OF MORPHOLOGICALLY RECONSTRUCTED CA3 HIPPOCAMPAL-NEURONS
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DOI：
10.1152/jn.1995.73.3.1157
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发表时间：
1995-03-01
影响因子：
2.5
通讯作者：
JOHNSTON, D
中科院分区：
文献类型：
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作者：
MIGLIORE, M;COOK, EP;JOHNSTON, D
1.我们测试了几个假设的机制和过程，控制的放电特性，并确定在CA 3海马神经元胞内钙的时空动态。具体而言，我们感兴趣的是：1）是否可以在使用许多已知离子电导的形态学现实模型中解释CA 3神经元的爆发和非爆发行为; 2）这种模型在不同的细胞形态中是否是稳健的; 3）爆发是否需要某些特定的非均匀分布的Ca 2+通道;以及4）这种模型是否可以再现从荧光成像研究确定的细胞内Ca 2+瞬变的幅度和空间分布，并且可以预测CA 3神经元的合理的细胞内Ca 2+浓度（[Ca 2 +]（i））分布。为此，我们已经开发了一个非常详细的模型，海马CA 3区爆发和nonbursting锥体神经元的膜离子通道的分布和密度。该模型再现了实验观察到的放电模式和细胞内Ca 2+的动力学。膜离子电导的动力学是基于可用的实验数据。该模型包括一个Na+通道，三个Ca 2+通道（Ca-N，Ca-L，Ca-T），三个Ca 2+非依赖性K+通道（K-DR，K-A，K-M），两个Ca 2+依赖性K+通道（K-C，K-AHP），以及细胞内Ca 2+相关过程如缓冲、泵送和径向扩散.为了测试该模型的鲁棒性，我们将其应用于六种不同的形态准确的重建CA 3海马锥体神经元。在每个神经元中，Ca 2+通道、Ca 2+相关过程和Ca 2+依赖性K+通道均匀分布于整个细胞。钙非依赖性K+通道位于索马和近端顶树突上。对于每个重建的细胞，我们能够再现爆发和非爆发放电特性以及体细胞和突触刺激的Ca 2+瞬变和分布。我们的模拟结果表明，CA 3锥体细胞爆裂行为不需要任何特殊的分布的钙离子依赖性通道和机制。此外，Ca 2+非依赖性K+电导的简单增加足以改变我们的CA 3神经元的放电模式从爆发到非爆发。该模型还显示与荧光成像数据一致的[Ca 2 +]（i）瞬变和分布。与体细胞刺激相比，非爆发模型的突触刺激的峰值[Ca 2 +]（i）分布更宽。与非爆发模型相比，爆发模型的躯体刺激显示[Ca 2 +]（i）的分布范围更广。两种模型中的突触刺激产生在刺激部位周围具有峰值的[Ca 2 +]（i）分布。总之，该模型能够使用几种重建的形态再现海马CA 3神经元的真实爆发、尖峰频率适应和[Ca 2 +]（i）动力学。在几乎所有的铸型中，只有在索马上和附近的钙离子非依赖性K+通道密度和分布的变化是必要的，以再现相同的电生理行为在不同的形态。不同模式的射击不依赖于不同的Ca 2+和Ca 2+依赖的K+通道分布，或对细胞的几何约束，但对Ca 2+的独立的K+通道的密度和分布上和附近的索马。然而，形态学因素，如细胞几何形状和树突状表面与体积比。确实影响[Ca 2 +]（i）瞬变和分布。
1. We tested several hypotheses with respect to the mechanisms and processes that control the firing characteristics and determine the spatial acid temporal dynamics of intracellular Ca2+ in CA3 hippocampal neurons. In particular, we were interested to know 1) whether bursting and nonbursting behavior of CA3 neurons could be accounted for in a morphologically realistic model using a number of the known ionic conductances; 2) whether such a model is robust across different cell morphologies; 3) whether some particular nonuniform distribution of Ca2+ channels is required for bursting; and 4) whether such a model can reproduce the magnitude and spatial distribution of intracellular Ca2+ transients determined from fluorescence imaging studies and can predict reasonable intracellular Ca2+ concentration ([Ca2+](i)) distribution for CA3 neurons.2. For this purpose we have developed a highly detailed model of the distribution and densities of membrane ion channels in hippocampal CA3 bursting and nonbursting pyramidal neurons. This model reproduces both the experimentally observed firing modes and the dynamics of intracellular Ca2+.3. The kinetics of the membrane ionic conductances are based on available experimental data. This model incorporates a single Na+ channel, three Ca2+ channels (Ca-N, Ca-L, and Ca-T), three Ca2+-independent K+ channels (K-DR, K-A, and K-M), two Ca2+-dependent K+ channels (K-C and K-AHP), and intracellular Ca2+-related processes such as bufffering, pumping, and radial diffusion.4. To test the robustness of the model, we applied it to six different morphologically accurate reconstructions of CA3 hippocampal pyramidal neurons. In every neuron, Ca2+ channels, Ca2+-related processes, and Ca2+-dependent K+ channels were uniformly distributed over the entire cell. Ca2+-independent K+ channels were placed on the soma and the proximal apical dendrites. For each reconstructed cell we were able to reproduce bursting and nonbursting firing characteristics as well as Ca2+ transients o and distributions for both somatic and synaptic stimulations.5. Our simulation results suggest that CA3 pyramidal cell bursting behavior does not require any special distribution of Ca2+-dependent channels and mechanisms. Furthermore, a simple increase in the Ca2+-independent K+ conductances is sufficient to change the firing mode of our CA3 neurons from bursting to nonbursting.6. The model also displays [Ca2+](i) transients and distributions that are consistent with fluorescent imaging data. Peak [Ca2+](i) distribution for synaptic stimulation of the nonbursting model is broader when compared with somatic stimulation. Somatic stimulation of the bursting model shows a broader distribution in [Ca2+](i) when compared with the nonbursting model. Synaptic stimulation in both models produces a [Ca2+](i) distribution that has a peak around the site of stimulation.7. In conclusion, this model is able to reproduce realistic bursting, spike Frequency adaptation, and [Ca2+](i) dynamics of hippocampal CA3 neurons using several reconstructed morphologies. In almost all casts changes only in the Ca2+-independent K+ channel densities and distributions on and near the soma were necessary to reproduce the same electrophysiological behavior in different morphologies. Different modes of firing were not dependent on varying Ca2+ and Ca2+-dependent K+ channel distribution, or on geometric constraints of the cell, but on Ca2+-independent K+ channel densities and distributions on and near the soma. Morphological factors such as cell geometry and dendritic surface-to-volume ratios, however. did influence [Ca2+](i) transients and distributions.