Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes
Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes
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DOI：
10.1371/journal.pcbi.1000886
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发表时间：
2010-08-01
影响因子：
4.3
通讯作者：
Nolan, Matthew F.
中科院分区：
文献类型：
--
作者：
Cannon, Robert C.;O'Donnell, Cian;Nolan, Matthew F.
神经元活动是通过改变离子通道开放和关闭状态之间的随机转换的概率来介导的。虽然形态学上的差异定义神经元细胞类型，并可能导致神经系统疾病，但对具有复杂形态的神经元中随机离子通道门控的影响知之甚少。我们介绍和验证新的计算工具，使有效的生成和模拟模型包含随机离子通道分布在树突和轴突膜。五种形态上不同的神经元细胞类型的比较表明，当所有模拟的神经元包含相同密度的随机离子通道，随机膜电位波动的幅度不同的细胞类型之间，并取决于亚细胞位置。对于典型的神经元，膜电位波动的幅度取决于通道动力学以及开放概率。使用一个详细的模型海马CA1区锥体神经元，我们表明，当内在离子通道门随机，树突或躯体尖峰的树突突触输入的启动概率在0和1之间不断变化，而当离子通道门确定性，概率是零或一。在生理放电率，随机门控的树突状离子通道几乎完全占概率体细胞和树突棘波产生的完全随机模型。这些结果表明，随机离子通道门控的后果不同的神经元细胞类型之间的全球和局部神经元隔室。而树突状神经元通常被认为是确定性的行为，我们的模拟表明，内在离子通道的随机门控的直接后果是，尖峰输出可能是一个概率函数的突触输入树突的模式。
Neuronal activity is mediated through changes in the probability of stochastic transitions between open and closed states of ion channels. While differences in morphology define neuronal cell types and may underlie neurological disorders, very little is known about influences of stochastic ion channel gating in neurons with complex morphology. We introduce and validate new computational tools that enable efficient generation and simulation of models containing stochastic ion channels distributed across dendritic and axonal membranes. Comparison of five morphologically distinct neuronal cell types reveals that when all simulated neurons contain identical densities of stochastic ion channels, the amplitude of stochastic membrane potential fluctuations differs between cell types and depends on sub-cellular location. For typical neurons, the amplitude of membrane potential fluctuations depends on channel kinetics as well as open probability. Using a detailed model of a hippocampal CA1 pyramidal neuron, we show that when intrinsic ion channels gate stochastically, the probability of initiation of dendritic or somatic spikes by dendritic synaptic input varies continuously between zero and one, whereas when ion channels gate deterministically, the probability is either zero or one. At physiological firing rates, stochastic gating of dendritic ion channels almost completely accounts for probabilistic somatic and dendritic spikes generated by the fully stochastic model. These results suggest that the consequences of stochastic ion channel gating differ globally between neuronal cell-types and locally between neuronal compartments. Whereas dendritic neurons are often assumed to behave deterministically, our simulations suggest that a direct consequence of stochastic gating of intrinsic ion channels is that spike output may instead be a probabilistic function of patterns of synaptic input to dendrites.