Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland.
Development. 2013 Jul;140(13):2823-7. doi: 10.1242/dev.091249. Epub 2013 May 29.
Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in the mammalian hippocampus. Newborn granule cells mature over several weeks to functionally integrate into the pre-existing neural circuitry. Even though an increasing number of genes that regulate neuronal polarization and neurite extension have been identified, the cellular mechanisms underlying the extension of neurites arising from newborn granule cells remain largely unknown. This is mainly because of the current lack of longitudinal observations of neurite growth within the endogenous niche. Here we used a novel slice culture system of the adult mouse hippocampal formation combined with in vivo retroviral labeling of newborn neurons and longitudinal confocal imaging to analyze the mode and velocity of neurite growth extending from immature granule cells. Using this approach we show that dendritic processes show a linear growth pattern with a speed of 2.19±0.2 μm per hour, revealing a much faster growth dynamic than expected by snapshot-based in vivo time series. Thus, we here identified the growth pattern of neurites extending from newborn neurons within their niche and describe a novel technology that will be useful to monitor neuritic growth in physiological and disease states that are associated with altered dendritic morphology, such as rodent models of epilepsy.
神经干细胞/祖细胞（NSPCs）在哺乳动物海马体中终生产生新的神经元。新生颗粒细胞在数周内成熟，以功能方式整合到预先存在的神经回路中。尽管已经鉴定出越来越多调节神经元极化和轴突延伸的基因，但新生颗粒细胞产生的轴突延伸的细胞机制在很大程度上仍然未知。这主要是因为目前缺乏对内源性龛位中轴突生长的纵向观察。在这里，我们使用了一种新的成年小鼠海马体切片培养系统，结合体内新生神经元逆转录病毒标记和纵向共聚焦成像，分析从未成熟颗粒细胞延伸的轴突的生长模式和速度。使用这种方法，我们发现树突状突起呈现线性生长模式，速度为每小时 2.19±0.2μm，比基于快照的体内时间序列所预期的生长动态快得多。因此，我们在这里确定了在其龛位中从新生神经元延伸的轴突的生长模式，并描述了一种新技术，该技术将有助于监测与树突形态改变相关的生理和疾病状态下的神经突生长，例如癫痫的啮齿动物模型。
