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GABA 能中间神经元谱系在出生后早期的发育过程中选择性地分选为特定的皮层层。

GABAergic interneuron lineages selectively sort into specific cortical layers during early postnatal development.

机构信息

Neuroscience Program and the Department of Cell Biology, Smilow Research Center, New York University School of Medicine, New York, NY 10016, USA.

出版信息

Cereb Cortex. 2011 Apr;21(4):845-52. doi: 10.1093/cercor/bhq155. Epub 2010 Aug 23.

Abstract

It is of considerable interest to determine how diverse subtypes of γ-aminobutyric acidergic (GABAergic) interneurons integrate into the functional network of the cerebral cortex. Using inducible in vivo genetic fate mapping approaches, we found that interneuron precursors arising from the medial ganglionic eminence (MGE) and caudal ganglionic eminence (CGE) at E12.5, respectively, populate deep and superficial cortical layers in a complementary manner in the mature cortex. These age-matched populations initiate tangential migration into the cortex simultaneously, migrate above and below the cortical plate in a similar ratio, and complete their entrance into the cortical plate by P1. Surprisingly, while these 2 interneuron populations show a comparable layer distribution at P1, they subsequently segregate into distinct cortical layers. In addition, the initiation of the radial sorting within each lineage coincided well with the upregulation of the potassium/chloride cotransporter KCC2. Moreover, layer sorting of a later born (E16.5) CGE-derived population occurred with a similar time course to the earlier born E12.5 cohorts, further suggesting that this segregation step is controlled in a subtype specific manner. We conclude that radial sorting within the early postnatal cortex is a key mechanism by which the layer-specific integration of GABAergic interneurons into the emerging cortical network is achieved.

摘要

确定不同亚型的γ-氨基丁酸能(GABAergic)中间神经元如何整合到大脑皮层的功能网络中是非常有趣的。使用可诱导的体内遗传命运映射方法,我们发现分别源自 E12.5 时的内侧神经节隆起(MGE)和尾状神经节隆起(CGE)的中间神经元前体细胞以互补的方式在成熟皮层中填充深和浅皮质层。这些年龄匹配的群体同时开始切线迁移到皮层中,以相似的比例在皮层板上方和下方迁移,并在 P1 之前完成进入皮层板的迁移。令人惊讶的是,虽然这 2 种中间神经元群体在 P1 时表现出相似的层分布,但随后它们会分离到不同的皮层层。此外,每个谱系内的放射状分选的开始与钾/氯离子共转运蛋白 KCC2 的上调很好地吻合。此外,较晚出生(E16.5)的 CGE 衍生群体的层分选与更早出生的 E12.5 群体的时间进程相似,进一步表明这种分离步骤以特定于亚型的方式进行控制。我们得出结论,早期产后皮层内的放射状分选是 GABAergic 中间神经元特异性整合到新兴皮层网络中的关键机制。

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