Can all axons regenerate in the absence of glial scar-mediated inhibition? Can axons elongate for distances sufficient to cover the lost output in the highly interconnected grey matter? Does the pattern of re-growth recapitulate developmental axon growth or does it employ a distinct growth program? And, finally, can axons reach the pre-lesion targets and form synapses? Answers to these questions are particularly important now that many experimental manipulations can successfully initiate axon regeneration in the adult injured central nervous system. In this paper, we examined these questions using 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, and found that:
- Many severed cortical axons in the grey matter can spontaneously regrow within weeks depending on cell type.
- Axons can extend for distances larger than the amount cut (i.e. distances unseen in the adult cortex) at speeds comparable to peripheral nerves.
- Injured axons grow monotonically, a pattern of growth which surprisingly differs from developmental axon growth.
- Regenerating axons consistently form new boutons to re-establish the pre-lesion synaptic densities but never reconnect to the original targets.
Our data unequivocally provide in vivo evidence for spontaneous axon regeneration in the mature brain and identify key underlying cellular and synaptic mechanisms.
Video – Animation of a serial section reconstruction used to identify a regenerating axon (in light blue) making a new connection (red) on a dendrite (grey) in the adult brain.
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