In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits
In-vivo single neuron axotomy triggers axon regeneration to restore synaptic density in specific cortical circuits
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DOI：
10.1038/ncomms3038
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发表时间：
2013-06-01
影响因子：
16.6
通讯作者：
De Paola, V.
中科院分区：
文献类型：
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作者：
Canty, A. J.;Huang, L.;De Paola, V.
在高度相互连接的灰质中，轴突如何以及何时对损伤做出反应，目前还知之甚少。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探索，在突触分辨率，在完整的大脑中的几个神经元群体的再生能力。对超过100个单独消融的轴突长达一年的时间推移分析显示，即使在神经胶质无疤痕的环境中，也无法再生。然而，取决于细胞类型，一些轴突自发地延伸未受损的成人皮质中看不到的距离，并且以与外周神经再生相当的最大速度延伸。再生遵循与发育轴突生长不同的模式。值得注意的是，虽然从来没有重新连接到原来的目标，轴突始终形成新的扣在可比的损伤前突触密度，这意味着内在的稳态程序的存在，调节再生轴突的突触数量。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。
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.