Kim Jeong-Ah, Koyama Ryuta, Yamada Ryuji X, Yamada Maki K, Nishiyama Nobuyoshi, Matsuki Norio, Ikegaya Yuji
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Cereb Cortex. 2004 Dec;14(12):1358-64. doi: 10.1093/cercor/bhh096. Epub 2004 Jun 10.
Dentate granule cells (DGCs) and their microcircuits have been implicated in hippocampus-dependent memory encoding and epileptogenesis. Little is known about how the proper maturation of DGCs is determined by their intrinsic programs or external factors during development. In order to explore this, we dispersed premature DGCs on living hippocampal slices. Here we report that the survival and network formation of DGCs are supported by local cues present in the dentate gyrus ex vivo. The density of surviving DGCs was almost uniform throughout the host slices 12 h after implantation but gradually became heterogenous across substrata, with the cells engrafted onto the stratum granulosum scoring the highest rate of survival. The mossy fiber axons arising from DGCs growing on this substratum were properly guided towards CA3, whereas other misplaced DGCs exhibited heterotopic axon projection. In particular, about half of the axons originating from the hilus were misguided into the molecular layer, which resembles the supragranular mossy fiber sprouting seen in epileptic disorders. These results suggest that local environmental factors influence the cell adhesion, neurite polarization and axon guidance of DGCs.
齿状颗粒细胞（DGCs）及其微回路与海马体依赖性记忆编码和癫痫发生有关。关于在发育过程中，DGCs的正常成熟是如何由其内在程序或外部因素决定的，我们知之甚少。为了探究这一点，我们将未成熟的DGCs分散在活的海马体切片上。在此我们报告，DGCs的存活和网络形成受到离体齿状回中存在的局部线索的支持。植入后12小时，存活的DGCs密度在整个宿主切片中几乎是均匀的，但随着时间推移，跨基质逐渐变得不均匀，移植到颗粒层的细胞存活率最高。源自生长在该基质上的DGCs的苔藓纤维轴突被正确地导向CA3，而其他位置不当的DGCs则表现出异位轴突投射。特别是，约一半源自齿状回门区的轴突被误导进入分子层，这类似于在癫痫疾病中看到的颗粒上苔藓纤维发芽。这些结果表明，局部环境因素会影响DGCs的细胞黏附、神经突极化和轴突导向。
