Glial cells promote muscle reinnervation by responding to activity-dependent postsynaptic signals.

After nerve injury, denervated synaptic sites in skeletal muscle commonly become reinnervated by sprouts that grow from nerve terminals on nearby muscle fibers. These terminal sprouts grow along a glial cell guide or "bridge" formed by Schwann cell (SC) processes that extend from denervated synaptic sites. Data presented here show that most bridges connect innervated and denervated synaptic sites rather than pairs of denervated sites even when most sites in the muscle are denervated. Furthermore, bridges are inhibited by presynaptic or postsynaptic blockade of synaptic transmission, manipulations that do not alter the extent of SC growth. These results show that an activity-dependent postsynaptic signal promotes the formation and/or maintenance of glial bridges and thus muscle reinnervation.

Schwann cells proliferate at rat neuromuscular junctions during development and regeneration.

Terminal Schwann cells (TSCs) cover neuromuscular junctions and are important in the repair and maintenance of these synapses. We have examined how these cells are generated at developing junctions and how their number is regulated during repair of nerve injury. At birth, approximately half of the junctions in rat soleus and extensor digitorum longus muscles have one TSC soma. Somata are absent from the remainder, although Schwann cell (SC) processes arising from somata along the preterminal axon cover almost all of these synapses. By 2 months of age, junctions have gained an additional two to three TSCs. Most of this gain occurs during the first 2 postnatal weeks and largely precedes the expansion of endplate size. Although the initial addition is caused by cell migration, mitotic labeling shows extensive division of TSCs at junctions. A slower addition of TSCs occurs in adult muscles, and TSC number in the adult is correlated with endplate size. During repair of nerve injury, TSC number is regulated by a combination of signals from motor neurons and denervated tissue. As shown previously (Connor et al., 1987), denervation of adult muscles did not, in itself, cause TSC mitosis. However, TSCs became mitotic during reinnervation. Partial denervation induced division of TSCs at innervated but not denervated endplates. A disproportionate number of these mitotic cells were found at endplates contacted by TSC processes extended from nearby denervated endplates, contacts known to promote nerve sprouting. These results show an association between TSC mitotic activity and alterations in synaptic structure during development, sprouting, and reinnervation.