Transplanted embryonic neurons integrate into adult neocortical circuits

Transplanted embryonic neurons integrate into adult neocortical circuits
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DOI:
10.1038/nature20113
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发表时间:
2016-11-10
期刊:
影响因子:
64.8
通讯作者:
Huebener, Mark
Huebener, Mark
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Falkner, Susanne;Grade, Sofia;Huebener, Mark

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成年哺乳动物大脑补偿因损伤或疾病造成的神经元丢失的能力非常有限。移植的目的是取代丢失的神经元,但新神经元可以在多大程度上整合到现有电路中尚不清楚。在这里,我们利用体内慢性双光子成像技术,证明了移植到成年小鼠视皮质的胚胎神经元通过选择性地修剪基础树突,成熟为真正的锥体细胞,在4-8周内达到了类似成人的树突棘和轴突密度。单突触追踪实验表明,移植的神经元接受与正常视觉皮质中锥体神经元的区域特异性传入输入相匹配的区域特异性传入输入,包括按地形组织的膝状体-皮质联系。此外,刺激选择性反应在数周的过程中不断提炼,最终变得与宿主神经元的反应难以区分。因此,移植的神经元可以非常特异地整合到新皮质回路中,而这些回路通常不会在成人大脑中整合新神经元。
The ability of the adult mammalian brain to compensate for neuronal loss caused by injury or disease is very limited. Transplantation aims to replace lost neurons, but the extent to which new neurons can integrate into existing circuits is unknown. Here, using chronic in vivo two-photon imaging, we show that embryonic neurons transplanted into the visual cortex of adult mice mature into bona fide pyramidal cells with selective pruning of basal dendrites, achieving adult-like densities of dendritic spines and axonal boutons within 4-8 weeks. Monosynaptic tracing experiments reveal that grafted neurons receive area-specific, afferent inputs matching those of pyramidal neurons in the normal visual cortex, including topographically organized geniculo-cortical connections. Furthermore, stimulus-selective responses refine over the course of many weeks and finally become indistinguishable from those of host neurons. Thus, grafted neurons can integrate with great specificity into neocortical circuits that normally never incorporate new neurons in the adult brain.