Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration. These heterotopic neuronal clusters significantly enhance the activity of the host circuits without causing epileptic seizures and attenuate the apoptotic injury-induced functional deficits in electrophysiological and behavioral tests. Chemogenetic activation of grafted neurons further improved functional recovery, and the persistence of the graft was necessary for maintaining restored functions in adult animals. Thus, implanting neuronal precursors capable to form synaptically integrated neuronal clusters combined with activation-based approaches represents a useful strategy for helping long-term functional recovery following brain injury.

中文翻译：

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移植的胚胎神经元通过增加受损皮层回路的活动来改善功能恢复。

损伤后适当的神经元前体移植是重建皮层回路的一种很有前景的策略，但这些方法的效率仍然有限。在这里，我们应用靶向细胞凋亡来选择性消融大鼠幼年大脑皮层中的 II/III 层锥体神经元，并尝试通过移植用适当的胚胎前体替换丢失的神经元。我们证明嫁接的前体不会迁移以替换丢失的神经元，而是形成血管化簇，与宿主网络建立相互的突触接触并显示功能整合。这些异位神经元簇在不引起癫痫发作的情况下显着增强了宿主回路的活性，并减轻了电生理和行为测试中细胞凋亡损伤引起的功能缺陷。移植神经元的化学遗传激活进一步改善了功能恢复，并且移植物的持久性对于维持成年动物恢复的功能是必要的。因此，植入能够形成突触整合神经元簇的神经元前体与基于激活的方法相结合，代表了一种有助于脑损伤后长期功能恢复的有用策略。