Biophysical basis of the phase response curve of subthalamic neurons with generalization to other cell types

Biophysical basis of the phase response curve of subthalamic neurons with generalization to other cell types
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DOI:
10.1152/jn.00054.2012
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发表时间:
2012-10-01
影响因子:
2.5
通讯作者:
Wilson, Charles J.
Wilson, Charles J.
中科院分区:
医学3区
文献类型:
--
作者:
Farries, Michael A.;Wilson, Charles J.

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Farries MA, Wilson CJ。丘脑下神经元相响应曲线的生物物理基础及对其他细胞类型的推广。[J]中国生物医学工程学报,2016,31(2):444 - 444。2012年7月11日首次发表;doi: 10.1152 / jn.00054.2012。-实验证据表明,丘脑下神经元对兴奋性突触后电位(EPSPs)的反应可以用它们的无穷小相响应曲线(iPRC)来描述。然而,控制iPRC形状的因素,从而控制丘脑下神经元对突触输入的反应方式,尚不清楚。我们开发了一个丘脑下神经元的生物物理模型,以帮助理解它们的iprc;该模型显示了许多丘脑下细胞共有的iPRC类型。我们设计了一种从其生物物理特性推导其iPRC的方法,该方法阐明了这些不同特性如何相互作用以形成iPRC。该方法揭示了为什么丘脑下神经元的反应很好地近似于它们的iprc,以及这种近似如何在强波动输入电流下变得不那么准确。它还将iPRC结构与细胞生理学的各个方面联系起来,这些方面可以通过简单的电流钳实验来估计。这使我们能够直接比较我们的理论预测的iPRC与从个体细胞对epsp或电流脉冲的响应中估计的iPRC。我们发现理论上预测的iprc与来自突触刺激的估计一致,但与来自体细胞电流注射的反应的估计不一致。突触电流与实验中在体细胞中应用的电流之间的差异可能是由于树突和轴突上电荷再分配动力学的差异。最终,我们的方法使我们能够确定新的方式,其中电压依赖性电导与AHP电导相互作用,影响突触整合,这将适用于广泛的细胞类型。
Farries MA, Wilson CJ. Biophysical basis of the phase response curve of subthalamic neurons with generalization to other cell types. J Neurophysiol 108: 1838-1855, 2012. First published July 11, 2012; doi: 10.1152/jn.00054.2012.-Experimental evidence indicates that the response of subthalamic neurons to excitatory postsynaptic potentials (EPSPs) is well described by their infinitesimal phase response curves (iPRC). However, the factors controlling the shape of that iPRC, and hence controlling the way subthalamic neurons respond to synaptic input, are unclear. We developed a biophysical model of subthalamic neurons to aid in the understanding of their iPRCs; this model exhibited an iPRC type common to many subthalamic cells. We devised a method for deriving its iPRC from its biophysical properties that clarifies how these different properties interact to shape the iPRC. This method revealed why the response of subthalamic neurons is well approximated by their iPRCs and how that approximation becomes less accurate under strong fluctuating input currents. It also connected iPRC structure to aspects of cellular physiology that could be estimated in simple current-clamp experiments. This allowed us to directly compare the iPRC predicted by our theory with the iPRC estimated from the response to EPSPs or current pulses in individual cells. We found that theoretically predicted iPRCs agreed well with estimates derived from synaptic stimuli, but not with those estimated from the response to somatic current injection. The difference between synaptic currents and those applied experimentally at the soma may arise from differences in the dynamics of charge redistribution on the dendrites and axon. Ultimately, our approach allowed us to identify novel ways in which voltage-dependent conductances interact with AHP conductances to influence synaptic integration that will apply to a wide range of cell types.