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首页> 美国卫生研究院文献>PLoS Computational Biology >Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons
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Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons

机译：丘脑皮质神经元的强直和爆发放电模式的受实验限制的生物物理模型

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Somatosensory thalamocortical (TC) neurons from the ventrobasal (VB) thalamus are central components in the flow of sensory information between the periphery and the cerebral cortex, and participate in the dynamic regulation of thalamocortical states including wakefulness and sleep. This property is reflected at the cellular level by the ability to generate action potentials in two distinct firing modes, called tonic firing and low-threshold bursting. Although the general properties of TC neurons are known, we still lack a detailed characterization of their morphological and electrical properties in the VB thalamus. The aim of this study was to build biophysically-detailed models of VB TC neurons explicitly constrained with experimental data from rats. We recorded the electrical activity of VB neurons (N = 49) and reconstructed morphologies in 3D (N = 50) by applying standardized protocols. After identifying distinct electrical types, we used a multi-objective optimization to fit single neuron electrical models (e-models), which yielded multiple solutions consistent with the experimental data. The models were tested for generalization using electrical stimuli and neuron morphologies not used during fitting. A local sensitivity analysis revealed that the e-models are robust to small parameter changes and that all the parameters were constrained by one or more features. The e-models, when tested in combination with different morphologies, showed that the electrical behavior is substantially preserved when changing dendritic structure and that the e-models were not overfit to a specific morphology. The models and their analysis show that automatic parameter search can be applied to capture complex firing behavior, such as co-existence of tonic firing and low-threshold bursting over a wide range of parameter sets and in combination with different neuron morphologies.
机译：腹侧丘脑（VB）丘脑的体感丘脑（TC）神经元是周围和大脑皮层之间的传感信息流的主要成分，并参与丘脑皮质状态（包括清醒和睡眠）的动态调节。通过在两种不同的发射模式（称为强音发射和低阈值爆发）中产生动作电位的能力，可以在细胞级别反映此属性。尽管TC神经元的一般特性是已知的，但我们仍然缺乏VB丘脑中它们的形态和电学特性的详细表征。这项研究的目的是建立明显受限于大鼠实验数据的VB TC神经元的生物物理详细模型。我们记录了VB神经元的电活动（N = 49），并通过应用标准化协议以3D形式重构了形态（N = 50）。在确定了不同的电学类型之后，我们使用了多目标优化来拟合单个神经元电学模型（e模型），从而产生了与实验数据一致的多种解决方案。使用拟合期间未使用的电刺激和神经元形态对模型进行了泛化测试。局部敏感性分析表明，电子模型对较小的参数更改具有鲁棒性，并且所有参数均受一个或多个功能的约束。当与不同形态结合进行测试时，电子模型表明当改变树枝状结构时，电行为基本上得以保留，并且电子模型并未过度适应特定的形态。模型及其分析表明，自动参数搜索可用于捕获复杂的放电行为，例如在广泛的参数集上并结合不同的神经元形态，进行强音放电和低阈值爆裂的并存。

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