Axons in the adult mammalian central nervous system (CNS) fail to regenerate inside out due to intrinsic and extrinsic neuronal determinants. During CNS development, axon growth, synapse formation, and function are tightly regulated processes allowing immature neurons to effectively grow an axon, navigate toward target areas, form synaptic contacts and become part of information processing networks that control behavior in adulthood. Not only immature neurons are able to precisely control the expression of a plethora of genes necessary for axon extension and pathfinding, synapse formation and function, but also non‐neuronal cells such as astrocytes and microglia actively participate in sculpting the nervous system through refinement, consolidation, and elimination of synaptic contacts. Recent evidence indicates that a balancing act between axon regeneration and synaptic function may be crucial for rebuilding functional neuronal circuits after CNS trauma and disease in adulthood. Here, we review the role of classical and new intrinsic and extrinsic neuronal determinants in the context of CNS development, injury, and disease. Moreover, we discuss strategies targeting neuronal and non‐neuronal cell behaviors, either alone or in combination, to promote axon regeneration and neuronal circuit formation in adulthood.

中文翻译：

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轴突生长和突触功能：中枢神经系统创伤和疾病中轴突再生和神经元回路形成的平衡作用。


由于内在和外在的神经元决定因素，成年哺乳动物中枢神经系统（CNS）中的轴突无法从内到外再生。在中枢神经系统发育过程中，轴突生长、突触形成和功能是受到严格调控的过程，使未成熟的神经元能够有效地生长轴突、导航到目标区域、形成突触接触并成为控制成年期行为的信息处理网络的一部分。不仅未成熟的神经元能够精确控制轴突延伸和寻路、突触形成和功能所需的大量基因的表达，而且星形胶质细胞和小胶质细胞等非神经元细胞也通过细化、巩固积极参与塑造神经系统，并消除突触接触。最近的证据表明，轴突再生和突触功能之间的平衡可能对于成年期中枢神经系统创伤和疾病后重建功能性神经元回路至关重要。在这里，我们回顾了经典和新的内在和外在神经元决定因素在中枢神经系统发育、损伤和疾病中的作用。此外，我们讨论了针对神经元和非神经元细胞行为的策略，无论是单独还是组合，以促进成年期的轴突再生和神经元回路形成。