Classic cadherins mediate selective intracortical circuit formation in the mouse neocortex

Classic cadherins mediate selective intracortical circuit formation in the mouse neocortex
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经典钙粘蛋白介导小鼠新皮质选择性皮质内回路形成

DOI:
10.1093/cercor/bhu197
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Ichikawa Y. and Kawasaki H.
Ichikawa Y. and Kawasaki H.
中科院分区:
医学2区
文献类型:
--
作者:
Wakimoto M.;Sehara K.;Ebisu H.;Hoshiba Y.;Tsunoda S.;Ichikawa Y. and Kawasaki H.

文献摘要

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了解选择性皮质内回路形成的分子机制是神经科学研究的重要问题之一。“桶网”是最近发现的源于初级体感觉(桶)皮层第4层2/3层神经元的皮质内轴突轨迹。第2/3层神经元轴突优先分布于第4层桶状皮质的间隔区,在那里它们表现出与须相关的模式。由于钙粘蛋白已被视为介导选择性神经元回路形成的潜在候选者,在这里我们研究了钙粘蛋白在桶状网形成中的作用。我们利用子宫电穿孔法表达显性阴性钙粘蛋白(dn-cadherin),破坏了钙粘蛋白的功能,发现桶状网受到严重破坏。共聚焦显微镜分析显示,dn-cadherin的表达降低了桶状皮质第4层间隔区轴突的密度。我们还发现,钙粘蛋白对桶状网的形成起着重要作用,而不是维持作用。我们的研究结果揭示了钙粘蛋白在新皮层局部皮层内回路形成中的重要作用。
Understanding the molecular mechanisms underlying the formation of selective intracortical circuitry is one of the important questions in neuroscience research. “Barrel nets” are recently identified intracortical axonal trajectories derived from layer 2/3 neurons in layer 4 of the primary somatosensory (barrel) cortex. Axons of layer 2/3 neurons are preferentially distributed in the septal regions of layer 4 of the barrel cortex, where they show whisker-related patterns. Because cadherins have been viewed as potential candidates that mediate the formation of selective neuronal circuits, here we examined the role of cadherins in the formation of barrel nets. We disrupted the function of cadherins by expressing dominant-negative cadherin (dn-cadherin) using in utero electroporation and found that barrel nets were severely disrupted. Confocal microscopic analysis revealed that expression of dn-cadherin reduced the density of axons in septal regions in layer 4 of the barrel cortex. We also found that cadherins were important for the formation, rather than the maintenance, of barrel nets. Our results uncover an important role of cadherins in the formation of local intracortical circuitry in the neocortex.