Channel density distributions explain spiking variability in the globus pallidus: a combined physiology and computer simulation database approach.
Channel density distributions explain spiking variability in the globus pallidus: a combined physiology and computer simulation database approach.
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通道密度分布解释了苍白球的尖峰变异：生理学和计算机模拟数据库相结合的方法。
DOI：
10.1523/jneurosci.4198-07.2008
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发表时间：
2008-07-23
期刊：
影响因子：
--
通讯作者：
Jaeger D
中科院分区：
文献类型：
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作者：
Günay C;Edgerton JR;Jaeger D
苍白球（GP）神经元记录在脑切片中表现出显着的内在电生理特性的变化。为了研究这种变异性是如何产生的，我们使用计算机模拟操纵GP神经元的生物物理特性。具体来说，我们创建了一个GP神经元模型数据库，其中包含100，602个模型，这些模型具有不同密度的九个膜电导，这些模型以复制典型生理数据的手动调整模型为中心。为了检验实验观察到的变异性可以归因于电导密度的变化这一假设，我们将我们的模型数据库结果与146个切片记录的生理数据库进行了比较。所产生的模型和记录的电生理特性进行了评估与相同的电流注入协议和分析与一组统一的措施，允许系统分析不同的电压门控和钙门控电导密度对测量的属性和模型和记录之间的详细比较的影响。我们的研究结果表明，大多数的实验变异性可以匹配不同的电导密度，我们证实了额外的部分块实验。进一步分析得到两个关键观察结果：（1）每个电压门控电导对多个测量值（如动作电位波形和自发或刺激尖峰频率）有影响;（2）每个电导的影响高度依赖于其他电导的背景背景。在某些情况下，这种相互作用可以逆转一个电导的密度对重要的兴奋性措施的影响。电导密度效应的这种背景依赖性对于理解通过影响离子通道起作用的药物和神经调节剂效应是重要的。
Globus pallidus (GP) neurons recorded in brain slices show significant variability in intrinsic electrophysiological properties. To investigate how this variability arises, we manipulated the biophysical properties of GP neurons using computer simulations. Specifically, we created a GP neuron model database with 100,602 models that had varying densities of nine membrane conductances centered on a hand-tuned model that replicated typical physiological data. To test the hypothesis that the experimentally observed variability can be attributed to variations in conductance densities, we compared our model database results to a physiology database of 146 slice recordings. The electrophysiological properties of generated models and recordings were assessed with identical current injection protocols and analyzed with a uniform set of measures, allowing a systematic analysis of the effects of varying voltage-gated and calcium-gated conductance densities on the measured properties and a detailed comparison between models and recordings. Our results indicated that most of the experimental variability could be matched by varying conductance densities, which we confirmed with additional partial block experiments. Further analysis resulted in two key observations: (1) each voltage-gated conductance had effects on multiple measures such as action potential waveform and spontaneous or stimulated spike rates; and (2) the effect of each conductance was highly dependent on the background context of other conductances present. In some cases, such interactions could reverse the effect of the density of one conductance on important excitability measures. This context dependence of conductance density effects is important to understand drug and neuromodulator effects that work by affecting ion channels.