In-vivo single neuron axotomy triggers axonregeneration to restore synaptic densityin specific cortical circuits

摘要

To what extent, how and when axons respond to injury in the highly interconnected greymatter is poorly understood. Here we use two-photon imaging and focused ion beam–scanning electron microscopy to explore, at synaptic resolution, the regrowth capacity ofseveral neuronal populations in the intact brain. Time-lapse analysis of 4100 individuallyablated axons for periods of up to a year reveals a surprising inability to regenerate even in aglial scar-free environment. However, depending on cell type some axons spontaneouslyextend for distances unseen in the unlesioned adult cortex and at maximum speeds comparableto peripheral nerve regeneration. Regrowth follows a distinct pattern from developmentalaxon growth. Remarkably, although never reconnecting to the original targets, axonsconsistently form new boutons at comparable prelesion synaptic densities, implying theexistence of intrinsic homeostatic programmes, which regulate synaptic numbers on regeneratingaxons. Our results may help guide future clinical investigations to promote functionalaxon regeneration.