A central role for denervated tissues in causing nerve sprouting

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Abstract
One of the oldest known forms of neuronal plasticity is the ability of peripheral nerves to grow and form functional connections after damage to neighbouring axons. Yet the source of the signal which elicits this "sprouting" remains unknown. In mammalian muscles, paralysis-which gives rise to many of the changes which occur in denervated muscles-causes motor nerve terminals to sprout. Could the inactive muscle fibres (rather than nerve degeneration products, another likely source) be responsible for some of the sprouting found in partial denervation? We confirm in this paper that direct stimulation of a partially denervated muscle inhibits sprouting and show that stimulation does so by activating the denervated fibres. Consequently after partial denervation the same signal as that which causes terminal sprouting in a paralysed muscle is able to spread from the denervated muscle fibres to the nerves on the innervated fibres and initiate terminal sprouting.