Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

终生神经发生和将新生神经元整合到成熟的神经元回路中都在哺乳动物脑的特殊壁ni中进行，并充当神经元替代策略的榜样。但是，成年后从未合并新神经元的剩余脑实质能够在多大程度上作为可塑性并容易容纳因损伤或神经系统疾病而遭受神经元损失的网络中的神经元呢？哪种微环境适合神经元置换和突触整合，哪些细胞表现最佳？是否可以恢复失去的功能，并且对现有电路的参与程度如何？异常连接会导致故障，尤其是在以兴奋性神经元为主的网络中，如大脑皮层？这些问题说明了连通性和电路方面对于再生医学的重要性，这是本综述的重点。我们将讨论神经元替代策略的令人印象深刻的进展以及来自外源和内源细胞源的成功。两者都已经看到了关键的新技术，例如突破性的诱导多能干细胞发现和直接的神经元重编程，为胎儿神经元的移植提供了替代方法，都预示着巨大的期望。为了使这些成为现实，神经元电路分析现在是关键。随着我们对神经元回路的了解增加，神经元替代疗法应满足大脑结构输入和输出中网络结构和功能的先决条件。