Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles

Abstract

1. 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 fibres and eleven motor units ranging in strength from 1 to 35% of the total muscle tension. 2. Individual units, regardless of starting size, were able to sprout by up to 5 times their normal size following interruption of one of the two spinal roots innervating the muscle. In practive this resulted in muscles which had three 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. 3. 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 fibres at the time regenerating axons reached the muscle. The re-innervating fibres grew to the original end-plate sites. 4. Following re-innervation the size of sprouted motor units apparently decreased. Thus, after re-innervation of muscles with three 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 fibres than normal, returning axons less than normal, and a small percentage of muscle fibres (ca. 10%) remained functionally innervated by axons of both sorts. 5. It is concluded that (i) in the mouse, axonal sprouting is a rapid and efficient process for restoring innervation; (ii) re-innervation of already innervated fibres can occur if the regenerating axons can return to existing end-plate sites; (iii) some of the redundant innervation is removed or repressed. 6. Possible mechanisms of competition between axon terminals are considered.