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Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity
PLOS Computational Biology ( IF 4.3 ) Pub Date : 2020-12-30 , DOI: 10.1371/journal.pcbi.1007937
Stefano Masoli , Alessandra Ottaviani , Stefano Casali , Egidio D’Angelo

The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.



中文翻译:

小脑高尔基细胞模型预测突触加工和突触可塑性的机制。

高尔基细胞是小脑颗粒层的主要抑制中间神经元。尽管最近的工作强调了其树突状组织和突触输入的复杂性,但这些神经元整合复杂输入模式的机制仍然未知。在这里,我们已经使用了8种详细的形态学重建方法来开发高尔基细胞的多室模型,其中Na,Ca和K通道沿着树突,体细胞,轴突起始节和轴突分布。这些模型忠实地再现了丰富的电生理和药理特性模式,并预测了这些神经元的运行机制。事实证明,与树突相比,基底树突与轴突初始节段的电连接更紧密。在突触传递过程中,平行纤维在根尖树突中引起缓慢的Ca依赖性去极化,从而增强了轴突初始节段编码器和Na-spike反向传播为基底树突,而抑制性突触有效地分流了反向传播电流。这种定向的树突加工过程建立了一个巧合检测器,可控制基底树突中依赖电压的NMDA受体解封,通过调节局部钙的流入,可为理论上预期的依赖于尖峰时间的可塑性提供基础。

更新日期:2020-12-31
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