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树突钠通道调节苍白球神经元的网络整合:一项建模研究。

Dendritic sodium channels regulate network integration in globus pallidus neurons: a modeling study.

机构信息

Department of Biology, Emory University, Atlanta, Georgia 30322, USA.

出版信息

J Neurosci. 2010 Nov 10;30(45):15146-59. doi: 10.1523/JNEUROSCI.2662-10.2010.

Abstract

The globus pallidus (GP) predominantly contains GABAergic projection neurons that occupy a central position in the indirect pathway of the basal ganglia. They have long dendrites that can extend through one-half the diameter of the GP in rats, potentially enabling convergence and interaction between segregated basal ganglia circuits. Because of the length and fine diameter of GP dendrites, however, it is unclear how much influence distal synapses have on spiking activity. Dendritic expression of fast voltage-dependent Na(+) channels (NaF channels) can enhance the importance of distal excitatory synapses by allowing for dendritic spike initiation and by subthreshold boosting of EPSPs. Antibody labeling has demonstrated the presence of NaF channel proteins in GP dendrites, but the quantitative expression density of the channels remains unknown. We built a series of nine GP neuron models that differed only in their dendritic NaF channel expression level to assess the functional impact of this parameter. The models were all similar in their basic electrophysiological features; however, higher expression levels of dendritic NaF channels increased the relative effectiveness of distal inputs for both excitatory and inhibitory synapses, broadening the effective extent of the dendritic tree. Higher dendritic NaF channel expression also made the neurons more resistant to tonic inhibition and highly sensitive to clustered synchronous excitation. The dendritic NaF channel expression pattern may therefore be a critical determinant of convergence for both the striatopallidal and subthalamopallidal projections, while also dictating which spatiotemporal input patterns are most effective at driving GP neuron output.

摘要

苍白球(GP)主要包含 GABA 能投射神经元,它们在基底神经节的间接通路中占据中心位置。它们的长树突可以在大鼠的 GP 中延伸穿过直径的一半,这可能使分离的基底神经节回路之间能够发生汇聚和相互作用。然而,由于 GP 树突的长度和细直径,尚不清楚远端突触对尖峰活动有多大影响。快速电压依赖性 Na(+) 通道(NaF 通道)的树突表达可以通过允许树突棘发起和 EPSP 的亚阈增强来增强远端兴奋性突触的重要性。抗体标记已经证明了 GP 树突中存在 NaF 通道蛋白,但通道的定量表达密度仍然未知。我们构建了一系列九个 GP 神经元模型,这些模型仅在其树突 NaF 通道表达水平上有所不同,以评估该参数的功能影响。这些模型在其基本电生理特征上都非常相似;然而,更高的树突 NaF 通道表达水平增加了远端输入对兴奋性和抑制性突触的相对有效性,扩大了树突的有效范围。更高的树突 NaF 通道表达还使神经元对紧张性抑制更具抗性,对簇状同步兴奋高度敏感。因此,树突 NaF 通道表达模式可能是纹状体苍白球和丘脑底苍白球投射的汇聚的关键决定因素,同时还决定了哪些时空输入模式最有效地驱动 GP 神经元输出。

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