Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065, USA.
J Comp Neurol. 2011 Apr 15;519(6):1196-218. doi: 10.1002/cne.22568.
Granule cell (GC) neurogenesis in the dentate gyrus (DG) does not always proceed normally. After severe seizures (e.g., status epilepticus [SE]) and some other conditions, newborn GCs appear in the hilus. Hilar ectopic GCs (EGCs) can potentially provide insight into the effects of abnormal location and seizures on GC development. Additionally, hilar EGCs that develop after SE may contribute to epileptogenesis and cognitive impairments that follow SE. Thus, it is critical to understand how EGCs differ from normal GCs. Relatively little morphometric information is available on EGCs, especially those restricted to the hilus. This study quantitatively analyzed the structural morphology of hilar EGCs from adult male rats several months after pilocarpine-induced SE, when they are considered to have chronic epilepsy. Hilar EGCs were physiologically identified in slices, intracellularly labeled, processed for light microscopic reconstruction, and compared to GC layer GCs, from both the same post-SE tissue and the NeuroMorpho database (normal GCs). Consistently, hilar EGC and GC layer GCs had similar dendritic lengths and field sizes, and identifiable apical dendrites. However, hilar EGC dendrites were topologically more complex, with more branch points and tortuous dendritic paths. Three-dimensional analysis revealed that, remarkably, hilar EGC dendrites often extended along the longitudinal DG axis, suggesting increased capacity for septotemporal integration. Axonal reconstruction demonstrated that hilar EGCs contributed to mossy fiber sprouting. This combination of preserved and aberrant morphological features, potentially supporting convergent afferent input to EGCs and broad, divergent efferent output, could help explain why the hilar EGC population could impair DG function.
颗粒细胞(GC)在齿状回(DG)的神经发生并不总是正常进行的。在严重的癫痫发作(例如癫痫持续状态[SE])和其他一些情况下,新生的 GC 会出现在门区。门区异位 GC(EGC)可以深入了解异常位置和癫痫发作对 GC 发育的影响。此外,SE 后发育的门区 EGC 可能导致 SE 后发生的癫痫发生和认知障碍。因此,了解 EGC 与正常 GC 的区别至关重要。关于 EGC 的形态计量学信息相对较少,尤其是那些仅限于门区的 EGC。本研究定量分析了毛果芸香碱诱导 SE 后几个月成年雄性大鼠门区 EGC 的结构形态,此时它们被认为患有慢性癫痫。在切片中对门区 EGC 进行生理鉴定,用细胞内标记物进行标记,进行光镜重建,并与来自同一 SE 组织和 NeuroMorpho 数据库(正常 GC)的 GC 层 GC 进行比较。一致的是,门区 EGC 和 GC 层 GC 的树突长度和场大小相似,并且可识别出顶树突。然而,门区 EGC 树突的拓扑结构更为复杂,具有更多的分支点和曲折的树突路径。三维分析表明,令人惊讶的是,门区 EGC 树突通常沿着 DG 的长轴延伸,这表明其具有增加的隔-颞整合能力。轴突重建表明,门区 EGC 参与了苔藓纤维发芽。这种保留和异常形态特征的组合,可能支持向 EGC 传入会聚输入和广泛发散的传出输出,有助于解释为什么门区 EGC 群体可能会损害 DG 的功能。