School of Computer and Communication Sciences and School of Life Sciences, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne EPFL, Switzerland.
J Neurophysiol. 2012 Mar;107(6):1756-75. doi: 10.1152/jn.00408.2011. Epub 2011 Dec 7.
Cortical information processing originates from the exchange of action potentials between many cell types. To capture the essence of these interactions, it is of critical importance to build mathematical models that reflect the characteristic features of spike generation in individual neurons. We propose a framework to automatically extract such features from current-clamp experiments, in particular the passive properties of a neuron (i.e., membrane time constant, reversal potential, and capacitance), the spike-triggered adaptation currents, as well as the dynamics of the action potential threshold. The stochastic model that results from our maximum likelihood approach accurately predicts the spike times, the subthreshold voltage, the firing patterns, and the type of frequency-current curve. Extracting the model parameters for three cortical cell types revealed that cell types show highly significant differences in the time course of the spike-triggered currents and moving threshold, that is, in their adaptation and refractory properties but not in their passive properties. In particular, GABAergic fast-spiking neurons mediate weak adaptation through spike-triggered currents only, whereas regular spiking excitatory neurons mediate adaptation with both moving threshold and spike-triggered currents. GABAergic nonfast-spiking neurons combine the two distinct adaptation mechanisms with reduced strength. Differences between cell types are large enough to enable automatic classification of neurons into three different classes. Parameter extraction is performed for individual neurons so that we find not only the mean parameter values for each neuron type but also the spread of parameters within a group of neurons, which will be useful for future large-scale computer simulations.
皮质信息处理源于许多细胞类型之间动作电位的交换。为了捕捉这些相互作用的本质,构建反映单个神经元中尖峰产生特征的数学模型至关重要。我们提出了一种从电流钳实验中自动提取这些特征的框架,特别是神经元的被动特性(即膜时间常数、反转电位和电容)、尖峰触发适应电流以及动作电位阈值的动力学。我们的最大似然方法产生的随机模型准确地预测了尖峰时间、亚阈值电压、发放模式和频率电流曲线的类型。提取三种皮质细胞类型的模型参数表明,细胞类型在尖峰触发电流和移动阈值的时间过程中表现出高度显著的差异,即它们的适应和不应期特性,但在被动特性方面没有差异。特别是,GABA 能快放电神经元仅通过尖峰触发电流介导弱适应,而常规放电兴奋性神经元通过移动阈值和尖峰触发电流共同介导适应。GABA 能非快放电神经元以降低的强度结合两种不同的适应机制。细胞类型之间的差异足够大,可以实现神经元的自动分类为三种不同的类别。为每个神经元提取参数,因此我们不仅找到了每个神经元类型的平均参数值,还找到了一组神经元中参数的分布,这对于未来的大规模计算机模拟将非常有用。