Conductance-based model of the voltage-dependent generation of a plateau potential in subthalamic neurons
Conductance-based model of the voltage-dependent generation of a plateau potential in subthalamic neurons
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DOI：
10.1152/jn.00508.2003
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发表时间：
2004-07-01
影响因子：
2.5
通讯作者：
Song, WJ
中科院分区：
文献类型：
--
作者：
Otsuka, T;Abe, T;Song, WJ
由于丘脑底核(STN)是基底神经节的驱动力，因此了解STN神经元的活动是如何调节的很重要。以前，我们已经报道了STN神经元的一个子集以一种电压依赖的方式产生平台电位。只有当细胞超极化时，这些平台电位才能被诱发。在这里，为了研究STN神经元平台电位的电压依赖性产生机制，我们在实验观察的基础上构建了基于电导的STN神经元平台产生模型，并将模拟结果与切片记录进行了比较。该模型由一个包含Na+电流、延迟整流性K+电流、A型K+电流、L样长时间钙电流、T型钙电流、钙依赖K+电流和泄漏电流的单室组成。我们的模拟结果表明，模型中的平台电位可以以一种电压依赖的方式诱导，这种方式依赖于L类长时间钙电流的失活特性。该模型还可以再现超极化电流注入终止后作为反弹电位的平台电位的产生。此外，我们测试了模拟平台电位对抑制性扰动的稳定性，发现该模型与脑片中STN神经元的平台电位具有类似的特性。在该模型中还检测了TEA阻断K+通道和BAPTA螯合细胞内钙离子对平台持续时间的影响，结果与实验结果一致。因此，我们的STN神经元模型可以定性地再现一些关于平台电位的实验观察。我们的结果表明，L钙通道的失活在电压依赖性平台电位的产生中起着重要作用。
Because the subthalamic nucleus (STN) acts as a driving force of the basal ganglia, it is important to know how the activities of STN neurons are regulated. Previously, we have reported that a subset of STN neurons generates a plateau potential in a voltage-dependent manner. These plateau potentials can be evoked only when the cell is hyperpolarized. Here, to examine the mechanism of the voltage-dependent generation of the plateau potential in STN neurons, we constructed a conductance-based model of the plateau-generating STN neuron based on experimental observations and compared simulation results with recordings in slices. The model consists of a single compartment containing a Na+ current, a delayed-rectifier K+ current, an A-type K+ current, an L-like long-lasting Ca2+ current, a T-type Ca2+ current, a Ca2+-dependent K+ current, and a leak current. Our simulation results showed that a plateau potential in the model could be induced in a voltage-dependent manner that depended on the inactivation properties of L-like longlasting Ca2+ current. The model could also reproduce the generation of a plateau potential as a rebound potential after termination of hyperpolarizing current injection. In addition, we tested the stability of simulated plateau potentials against inhibitory perturbation and found that the model showed similar properties observed for the plateau potentials of STN neurons in slices. The effects of K+ channel blockade by TEA and intracellular Ca2+ ion chelation by BAPTA on the plateau duration were also tested in the model and were found to match experimental observations. Thus our STN neuron model could qualitatively reproduce a number of experimental observations on plateau potentials. Our results suggest that the inactivation of L-type Ca2+ channels plays an important role in the voltage-dependent generation of the plateau potential.