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从计算上探索实验无法到达的领域:在类状态下对树突离子通道电流进行动力学评估。

Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during -like states.

机构信息

Krembil Research Institute, University Health Network, Toronto, ON, M5T 0S8, Canada.

Department of Physiology, University of Toronto, Toronto, ON, Canada.

出版信息

F1000Res. 2020 Mar 11;9:180. doi: 10.12688/f1000research.22584.2. eCollection 2020.

Abstract

Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments . The picture that we do have is largely based on somatic recordings performed . Uncovering ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means. We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create -like states for these cellular models by including levels of synaptic bombardment that would occur . Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models. We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between and -like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during -like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal. Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking. Simultaneous access to dendritic compartments during simulated states shows that the magnitudes of some ion channel current contributions are differentially altered during -like states relative to .

摘要

尽管技术取得了进步,但特定细胞类型如何参与大脑功能仍然是一个谜。此外,对于不同离子通道电流对不同神经元亚型及其树突隔室的细胞兴奋性的贡献知之甚少。我们目前所拥有的图景主要基于躯体记录。使用纯粹的实验手段,揭示在神经元亚型中离子通道电流的贡献,这些亚型在神经元群体中只占少数,目前还不是一项可行的任务。

我们采用了两种形态详细的多隔室模型,分别代表特定类型的抑制性中间神经元,即齿状回腔隙分子(OLM)细胞。OLM 细胞是 CA1 海马体中研究得很好的细胞类型,对于门控感觉和上下文信息很重要。我们通过包括可能发生的突触轰炸水平,为这些细胞模型创建类似的状态。使用可视化工具和分析,我们评估模型不同体部和树突隔室的离子通道电流贡献分布。

我们确定了在类似和状态之间的树突兴奋性、离子通道电流贡献和共同激活模式的变化。主要发现是,在状态之间,离子通道电流之间的相对定时基本不变,但在大小上发生变化,并在树突隔室中传播减少。我们还发现,在类似状态下,树突超极化激活环核苷酸门控通道(h 通道)的激活增强,这表明位于树突上的 h 通道在改变行为动物中的信号传播方面具有功能重要性。

总的来说,我们使用计算建模演示了控制神经元放电的离子通道机制可能发生的动态变化。在模拟的状态期间同时访问树突隔室表明,在类似状态下,相对于状态,一些离子通道电流贡献的幅度发生了差异改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b24c/7309568/69d8f3898406/f1000research-9-27205-g0000.jpg

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