Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: A network model of the dentate gyrus incorporating cell types and axonal topography
Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: A network model of the dentate gyrus incorporating cell types and axonal topography
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DOI：
10.1152/jn.00777.2004
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发表时间：
2005-01-01
影响因子：
2.5
通讯作者：
Soltesz, I
中科院分区：
文献类型：
--
作者：
Santhakumar, V;Aradi, I;Soltesz, I
苔藓细胞丢失和苔藓纤维发芽是反复癫痫发作和头部创伤的两个典型后果。然而，它们对超激发态的精确贡献还没有很好的理解。因为这是困难的，往往是不可能的，独立检查使用实验技术是否是苔藓细胞的损失或苔藓纤维的发芽，导致齿状回过度兴奋，我们建立了一个生物病理学现实和解剖学代表性的计算模型的齿状回来研究这个问题。527细胞模型，包含颗粒、苔藓、篮状和门细胞，轴突投射到穿通通路终止区，表明即使是微弱的苔藓纤维发芽（在癫痫的毛果芸香碱模型中观察到的10 - 15%的强发芽）导致癫痫发作的扩散，在局灶性刺激穿通通路后，在体内研究中报道的发芽苔藓纤维接触的层状分布是维持网络中类似苔藓的活性的重要因素。相反，强大的超兴奋性诱导苔藓纤维发芽的影响，去除苔藓细胞导致颗粒细胞的反应降低穿孔通路激活与最近的实验数据。这些结果表明，即使在只有相对较弱的苔藓纤维发芽的情况下，如中度脑震荡实验性头部损伤后的情况下，苔藓纤维发芽的关键作用。
Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting ( 10 - 15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. The simulations also indicated that the spatially restricted, lamellar distribution of the sprouted mossy fiber contacts reported in in vivo studies was an important factor in sustaining seizure-like activity in the network. In contrast to the robust hyperexcitability-inducing effects of mossy fiber sprouting, removal of mossy cells resulted in decreased granule cell responses to perforant-path activation in agreement with recent experimental data. These results indicate the crucial role of mossy fiber sprouting even in situations where there is only relatively weak mossy fiber sprouting as is the case after moderate concussive experimental head injury.