Peng Zechun, Houser Carolyn R
Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
J Neurosci. 2005 Aug 3;25(31):7210-20. doi: 10.1523/JNEUROSCI.0838-05.2005.
Identifying the brain regions and neuronal cell types that become active at the time of spontaneous seizures remains an important challenge for epilepsy research, and the involvement of dentate granule cells in early seizure events continues to be debated. Although Fos expression is commonly used to evaluate patterns of neuronal activation, there have been few studies of Fos localization after spontaneous seizures. Thus, in a pilocarpine model of recurrent seizures in C57BL/6 mice, Fos expression was examined at multiple time points after spontaneous seizures to follow the temporal and spatial patterns of Fos activation. By 15 min after the beginning of a spontaneous behavioral seizure, Fos labeling was evident in dentate granule cells. This labeling was particularly striking because of its wide extent and relatively uniform appearance in the granule cell layer. At later time points, from 30 min to 4 h after a spontaneous seizure, Fos labeling was also detected in interneurons within the dentate gyrus and in widespread regions of the temporal lobe. Interestingly, the timing of Fos activation appeared to differ among different types of GABAergic interneurons in the dentate gyrus, with labeling of parvalbumin neurons along the base of the granule cell layer preceding that of GABA neurons in the molecular layer. The findings in this mouse model are consistent with previous suggestions that spontaneous seizures in temporal lobe epilepsy may result from a periodic breakdown of the normal filter functions of the dentate gyrus and a resulting increase in hypersynchronous activity of dentate granule cells.
确定在自发性癫痫发作时活跃的脑区和神经元细胞类型仍然是癫痫研究的一项重要挑战，齿状颗粒细胞在早期癫痫发作事件中的作用仍存在争议。虽然Fos表达通常用于评估神经元激活模式，但关于自发性癫痫发作后Fos定位的研究却很少。因此，在C57BL/6小鼠的匹鲁卡品复发性癫痫模型中，在自发性癫痫发作后的多个时间点检查Fos表达，以追踪Fos激活的时空模式。在自发性行为性癫痫发作开始后15分钟，齿状颗粒细胞中可见Fos标记。这种标记特别显著，因为它在颗粒细胞层中的范围广泛且外观相对均匀。在随后的时间点，即自发性癫痫发作后30分钟至4小时，在齿状回内的中间神经元以及颞叶的广泛区域也检测到Fos标记。有趣的是，齿状回中不同类型的GABA能中间神经元的Fos激活时间似乎有所不同，颗粒细胞层底部的小白蛋白神经元的标记先于分子层中的GABA神经元。该小鼠模型中的发现与先前的观点一致，即颞叶癫痫的自发性发作可能是由于齿状回正常过滤功能的周期性破坏以及齿状颗粒细胞超同步活动的增加所致。
