Stochastic Calcium Mechanisms Cause Dendritic Calcium Spike Variability
Stochastic Calcium Mechanisms Cause Dendritic Calcium Spike Variability
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DOI：
10.1523/jneurosci.1722-13.2013
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发表时间：
2013-10-02
影响因子：
5.3
通讯作者：
De Schutter, Erik
中科院分区：
文献类型：
--
作者：
Anwar, Haroon;Hepburn, Iain;De Schutter, Erik
树突状钙峰的爆发在许多类型神经元的兴奋性和突触可塑性中起重要作用。在单个浦肯野细胞中，自发的和突触诱发的树突状钙爆发具有各种形状和不同数量的尖峰。造成这种变化的机制从未被彻底调查。在这项研究中，一个详细的计算模型，使用新的模拟例程，以确定随机离子通道，离子通道的空间排列，和随机细胞内钙产生钙爆发变异的作用。与大鼠的实验记录一致，在模拟中观察到爆发形状的强烈变化。这种变异性在大模型尺寸中持续存在，与仅包含电压门控通道的模型相反，其中变异性随着系统尺寸的增加而迅速降低。Hodgkin-Huxley尖峰和钙爆发的相平面分析确定了概率相边界周围的相空间波动作为确定模型大小的可变性的依赖性的机制。随机钙动力学是钙爆发波动的主要原因，特别是钙激活的mkB/BK型和SK 2通道。钙浓度的局部变异性在较大的模型尺寸下具有显著影响。在重建的树突中的自发和突触诱发的钙爆发的模拟显示，此外，强大的空间和时间的电压和钙的变化，取决于树突的形态学特性。我们的研究结果表明，随机细胞内钙机制在树突状细胞钙峰的产生中起着至关重要的作用，因此在神经元的兴奋性和可塑性的研究中是一个重要的考虑因素。
Bursts of dendritic calcium spikes play an important role in excitability and synaptic plasticity in many types of neurons. In single Purkinje cells, spontaneous and synaptically evoked dendritic calcium bursts come in a variety of shapes with a variable number of spikes. The mechanisms causing this variability have never been investigated thoroughly. In this study, a detailed computational model using novel simulation routines is applied to identify the roles that stochastic ion channels, spatial arrangements of ion channels, and stochastic intracellular calcium have toward producing calcium burst variability. Consistent with experimental recordings from rats, strong variability in the burst shape is observed in simulations. This variability persists in large model sizes in contrast to models containing only voltage-gated channels, where variability reduces quickly with increase of system size. Phase plane analysis of Hodgkin-Huxley spikes and of calcium bursts identifies fluctuation in phase space around probabilistic phase boundaries as the mechanism determining the dependence of variability on model size. Stochastic calcium dynamics are the main cause of calcium burst fluctuations, specifically the calcium activation of mslo/BK-type and SK2 channels. Local variability of calcium concentration has a significant effect at larger model sizes. Simulations of both spontaneous and synaptically evoked calcium bursts in a reconstructed dendrite show, in addition, strong spatial and temporal variability of voltage and calcium, depending on morphological properties of the dendrite. Our findings suggest that stochastic intracellular calcium mechanisms play a crucial role in dendritic calcium spike generation and are therefore an essential consideration in studies of neuronal excitability and plasticity.