Using multi-compartment ensemble modeling as an investigative tool of spatially distributed biophysical balances: application to hippocampal oriens-lacunosum/moleculare (O-LM) cells.
Using multi-compartment ensemble modeling as an investigative tool of spatially distributed biophysical balances: application to hippocampal oriens-lacunosum/moleculare (O-LM) cells.
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DOI：
10.1371/journal.pone.0106567
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Skinner FK
中科院分区：
文献类型：
--
作者：
Sekulić V;Lawrence JJ;Skinner FK
神经元的多室模型提供了深入了解树突复杂的综合特性。由于通过实验确定每个神经元室中每种通道类型的确切密度和动力学是不可行的，因此开发模型的一个基本目标是帮助表征这些特性。为了解决给定神经元类型中固有的生物变异性，已经从使用手动调整模型转向使用模型的集合或种群。在集体捕获神经元的输出时，集成建模方法揭示了控制神经元动力学的重要电导平衡。然而，对于给定的神经元类型，密度，动力学和分布而言，电导从未完全已知。因此，任何多室模型都是不完整的。在这项工作中，我们的主要目标是使用集成建模作为神经元生物物理平衡的研究工具，其中实验和模型之间的循环从一开始就是设计标准。我们考虑了定向-空洞/分子（O-LM）中间神经元，这是一种突出的中间神经元亚型，在海马的信息流中起着重要的门控作用。O-LM细胞表达超极化激活电流（I h）。尽管树突I - h可能对O-LM细胞的整合特性有重要影响，但I - h在O-LM树突上的区室分布尚不清楚。使用高性能计算集群，我们生成了一个模型数据库，其中包括有或没有树突I h的模型。我们使用了九种不同电导类型的电导值范围，并探索了不同的电导形态。与O-LM细胞电生理特性数据集相比，模型被量化并基于最小误差进行排名。揭示了电导之间的共调节平衡，其中两个依赖于树突I h的存在。这些发现为未来区分体细胞和树突I h的实验提供了信息，从而继续模型和实验之间的循环。
Multi-compartmental models of neurons provide insight into the complex, integrative properties of dendrites. Because it is not feasible to experimentally determine the exact density and kinetics of each channel type in every neuronal compartment, an essential goal in developing models is to help characterize these properties. To address biological variability inherent in a given neuronal type, there has been a shift away from using hand-tuned models towards using ensembles or populations of models. In collectively capturing a neuron's output, ensemble modeling approaches uncover important conductance balances that control neuronal dynamics. However, conductances are never entirely known for a given neuron class in terms of its types, densities, kinetics and distributions. Thus, any multi-compartment model will always be incomplete. In this work, our main goal is to use ensemble modeling as an investigative tool of a neuron's biophysical balances, where the cycling between experiment and model is a design criterion from the start. We consider oriens-lacunosum/moleculare (O-LM) interneurons, a prominent interneuron subtype that plays an essential gating role of information flow in hippocampus. O-LM cells express the hyperpolarization-activated current (I h). Although dendritic I h could have a major influence on the integrative properties of O-LM cells, the compartmental distribution of I h on O-LM dendrites is not known. Using a high-performance computing cluster, we generated a database of models that included those with or without dendritic I h. A range of conductance values for nine different conductance types were used, and different morphologies explored. Models were quantified and ranked based on minimal error compared to a dataset of O-LM cell electrophysiological properties. Co-regulatory balances between conductances were revealed, two of which were dependent on the presence of dendritic I h. These findings inform future experiments that differentiate between somatic and dendritic I h, thereby continuing a cycle between model and experiment.
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DOI：
10.1523/jneurosci.2662-10.2010
发表时间：
2010-11-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Edgerton JR;Hanson JE;Günay C;Jaeger D
通讯作者：
Jaeger D
影响因子：
16.2
作者：
Gidon, Albert;Segev, Idan
通讯作者：
Segev, Idan
影响因子：
2.9
作者：
Hasselmo, ME;Bodelón, C;Wyble, BP
通讯作者：
Wyble, BP
DOI：
10.1523/jneurosci.6062-10.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Edgerton JR;Jaeger D
通讯作者：
Jaeger D
影响因子：
2.5
作者：
Berger, T;Larkum, ME;Lüscher, HR
通讯作者：
Lüscher, HR