MRC Clinical Science Centre, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
Nat Commun. 2013;4:2038. doi: 10.1038/ncomms3038.
To what extent, how and when axons respond to injury in the highly interconnected grey matter is poorly understood. Here we use two-photon imaging and focused ion beam-scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity of several neuronal populations in the intact brain. Time-lapse analysis of >100 individually ablated axons for periods of up to a year reveals a surprising inability to regenerate even in a glial scar-free environment. However, depending on cell type some axons spontaneously extend for distances unseen in the unlesioned adult cortex and at maximum speeds comparable to peripheral nerve regeneration. Regrowth follows a distinct pattern from developmental axon growth. Remarkably, although never reconnecting to the original targets, axons consistently form new boutons at comparable prelesion synaptic densities, implying the existence of intrinsic homeostatic programmes, which regulate synaptic numbers on regenerating axons. Our results may help guide future clinical investigations to promote functional axon regeneration.
轴突在高度相互连接的灰质中对损伤的反应程度、方式和时间尚不清楚。在这里，我们使用双光子成像和聚焦离子束扫描电子显微镜，以突触分辨率探索完整大脑中几种神经元群体的再生能力。对长达一年的>100 个单独消融的轴突进行时程分析表明，即使在没有神经胶质瘢痕的环境中，轴突也几乎没有再生能力。然而，根据细胞类型的不同，一些轴突会自发延伸，延伸距离超过未损伤成年皮质中的距离，最大速度可与周围神经再生相媲美。再生遵循与发育性轴突生长明显不同的模式。值得注意的是，尽管从未重新连接到原始靶点，但轴突始终在可比的损伤前突触密度处形成新的末梢，这意味着存在内在的稳态程序，调节再生轴突上的突触数量。我们的研究结果可能有助于指导未来的临床研究，以促进功能性轴突再生。
