Transcriptomics of critical period of visual cortical plasticity in mice
Transcriptomics of critical period of visual cortical plasticity in mice
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DOI：
10.1073/pnas.1509323112
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发表时间：
2015-06-30
影响因子：
11.1
通讯作者：
Rakic, Pasko
中科院分区：
文献类型：
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作者：
Benoit, Jamie;Ayoub, Albert E.;Rakic, Pasko
与大脑皮层的产前发育相反，当细胞产生、迁移和层形成占主导地位时，出生后的发育涉及更微妙的过程，例如活动依赖性可塑性，包括通过稳定和消除来细化突触连接。在本研究中，我们使用高空间分辨率的RNA-seq来检查小鼠视觉皮层2/3、4、5和6层在可塑性关键期[出生后第5天（P5）]开始前、高峰期（P26）和成熟期（P180）的差异基因表达，并将其与前额叶关联区域进行比较。我们发现，尽管参与细胞分裂、神经元迁移和轴突引导等早期发育事件的基因在 P5 时仍然很突出，但它们的表达在 P26 时大部分终止，此时突触可塑性和相关信号通路变得丰富。出乎意料的是，这个年龄段两个区域的基因表达谱相似，表明视觉皮层和关联皮层之间的活动依赖性可塑性受到相同的遗传限制。尽管基因表达变化在 P26 之前遵循相似的路径，但我们已经确定了 30 个在关键时期突出的区域富集基因。在 P180，尽管基因表达差异水平有所下降，我们还是鉴定出了数百个差异表达的基因同工型。这一结果表明，一旦遗传发育程序停止，剩余的形态发生过程可能取决于翻译后事件。
In contrast to the prenatal development of the cerebral cortex, when cell production, migration, and layer formation dominate, development after birth involves more subtle processes, such as activity-dependent plasticity that includes refinement of synaptic connectivity by its stabilization and elimination. In the present study, we use RNA-seq with high spatial resolution to examine differential gene expression across layers 2/3, 4, 5, and 6 of the mouse visual cortex before the onset of the critical period of plasticity [postnatal day 5 (P5)], at its peak (P26), and at the mature stage (P180) and compare it with the prefrontal association area. We find that, although genes involved in early developmental events such as cell division, neuronal migration, and axon guidance are still prominent at P5, their expression largely terminates by P26, when synaptic plasticity and associated signaling pathways become enriched. Unexpectedly, the gene expression profile was similar in both areas at this age, suggesting that activity-dependent plasticity between visual and association cortices are subject to the same genetic constraints. Although gene expression changes follow similar paths until P26, we have identified 30 regionally enriched genes that are prominent during the critical period. At P180, we identified several hundred differentially expressed gene isoforms despite subsiding levels of gene expression differences. This result indicates that, once genetic developmental programs cease, the remaining morphogenetic processes may depend on posttranslational events.