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哺乳动物外毛细胞的计算模型。

A Computational model of the mammalian external tufted cell.

机构信息

University of Utah, Department of Mathematics, 155 S 1400 E, Salt Lake City, Utah 84112, United States.

出版信息

J Theor Biol. 2019 Feb 7;462:109-121. doi: 10.1016/j.jtbi.2018.10.003. Epub 2018 Oct 2.

Abstract

We introduce a novel detailed conductance-based model of the bursting activity in external tufted (ET) cells of the olfactory bulb. We investigate the mechanisms underlying their bursting, and make experimentally-testable predictions. The ionic currents included in the model are specific to ET cells, and their kinetic and other parameters are based on experimental recordings. We validate the model by showing that its bursting characteristics under various conditions (e.g. blocking various currents) are consistent with experimental observations. Further, we identify the bifurcation structure and dynamics that explain bursting behavior. This analysis allows us to make predictions of the response of the cell to current pulses at different burst phases. We find that depolarizing (but not hyperpolarizing) inputs received during the interburst interval can advance burst timing, creating the substrate for synchronization by excitatory connections. It has been hypothesized that such synchronization among the ET cells within one glomerulus might help coordinate the glomerular output. Next we investigate model parameter sensitivity and identify parameters that play the most prominent role in controlling each burst characteristic, such as the burst frequency and duration. Finally, the response of the cell to periodic inputs is examined, reflecting the sniffing-modulated input that these cell receive in vivo. We find that individual cells can be better entrained by inputs with higher, rather than lower, frequencies than the intrinsic bursting frequency of the cell. Nevertheless, a heterogeneous population of ET cells (as may be found in a glomerulus) is able to produce reliable periodic population responses even at lower input frequencies.

摘要

我们介绍了一种新颖的详细的基于电导的嗅球外丛状(ET)细胞爆发活动模型。我们研究了它们爆发的机制,并做出了可进行实验验证的预测。该模型中包含的离子电流是 ET 细胞特有的,其动力学和其他参数是基于实验记录的。我们通过展示模型在各种条件下(例如阻断各种电流)的爆发特征与实验观察结果一致,验证了该模型的有效性。此外,我们确定了解释爆发行为的分岔结构和动力学。这种分析使我们能够对细胞在不同爆发相位下对电流脉冲的响应进行预测。我们发现,在爆发间隔期间接收到的去极化(而非超极化)输入可以提前爆发定时,为兴奋性连接的同步创造了基础。有人假设,一个肾小球内的 ET 细胞之间的这种同步可能有助于协调肾小球的输出。接下来,我们研究了模型参数的敏感性,并确定了控制每个爆发特征的最重要的参数,例如爆发频率和持续时间。最后,我们研究了细胞对周期性输入的反应,反映了这些细胞在体内接收到的嗅探调制输入。我们发现,与细胞固有爆发频率相比,输入频率较高而非较低的输入可以更好地使单个细胞同步。然而,即使在较低的输入频率下,具有不同特性的 ET 细胞群体(可能在一个肾小球中发现)也能够产生可靠的周期性群体反应。

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