Dendritic sodium channels regulate network integration in globus pallidus neurons: a modeling study.
Dendritic sodium channels regulate network integration in globus pallidus neurons: a modeling study.
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DOI：
10.1523/jneurosci.2662-10.2010
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发表时间：
2010-11-10
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影响因子：
--
通讯作者：
Jaeger D
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文献类型：
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作者：
Edgerton JR;Hanson JE;Günay C;Jaeger D
苍白球 (GP) 主要包含 GABA 能投射神经元，在基底节间接通路中占据中心位置。它们具有长树突，可以延伸穿过大鼠 GP 直径的一半，有可能实现分离的基底神经节回路之间的汇聚和相互作用。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尖峰启动和 EPSP 的阈下增强来增强远端兴奋性突触的重要性。抗体标记已证明 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 9 个 GP 神经元模型，这些模型仅在树突 NaF 通道表达水平上有所不同，以评估该参数的功能影响。这些模型的基本电生理特征都很相似；然而，树突NaF通道的较高表达水平增加了兴奋性和抑制性突触远端输入的相对有效性，扩大了树突树的有效范围。较高的树突 NaF 通道表达也使神经元对强直抑制具有更强的抵抗力，并对集群同步激发高度敏感。因此，树突 NaF 通道表达模式可能是纹状体苍白球和丘脑下苍白球投影收敛的关键决定因素，同时也决定了哪种时空输入模式在驱动 GP 神经元输出方面最有效。
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 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 9 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.