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.