Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles.

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Abstract
The capacity of motor units to sprout after partial denervation and the ability of regenerating axons to suppress newly formed sprouts was examined in mouse skeletal muscle. Most experiments were performed on the peroneus tertius muscle which has 300 muscle fibers and 11 motor units ranging in strength from 1 to 35% of the total muscle tension. Individual units, regardless of starting size, were able to sprout by up to 5.times. their normal size following interruption of 1 of the 2 spinal roots innervating the muscle. In practice this resulted in muscles which had 3 or more units left intact becoming completely innervated again within 12 days. The majority of the sprouts probably innervated the old denervated end-plate sites.. In the absence of re-innervation by the severed motor axons the sprouts persisted. In peroneus tertius about 60% of the sprouts giving rise to end-plates arose terminally and 40% collaterally. In soleus almost all the sprouts were terminal. Re-innervation of the muscle by the severed motor axons occurred, starting from 14 days onwards after a crush injury, 19 days onwards after a cut. Re-innervation occurred even in muscles which presumably had no remaining denervated muscle fibers at the time regenerating axons reached the muscle. The re-innervating fibers grew to the original end-plate sites. Following re-innervation the size of sprouted motor units apparently decreased. Thus, after re-innervation of muscles with 3 or more sprouted motor units, the sprouted units no longer caused contraction of all the muscle. However, the normal state of the muscle was not restored and the sprouted units continued to innervate more muscle fibers than normal, returning axons less than normal, and a small percentage of muscle fibers (about 10%) remained functionally innervated by axons of both sorts. In the mouse, axonal sprouting is a rapid and efficient process for restoring innervation; re-innervation of already innervated fibers can occur if the regenerating axons can return to existing end-plate sites; some of the redundant innervation is removed or repressed. Possible mechanisms of competition between axon terminals are considered.