Electrical activity and postsynapse formation in adult muscle: gamma-AChRsare not required

Skeletal muscle fibers will not accept hyperinnervation by foreign motor ax ons unless they are paralyzed, suggesting that paralysis makes them recepti ve to innervation, e.g., by upregulating extrasynaptic expression of gamma -AChRs and/or of the agrin receptor MuSK. To examine the involvement of the se parameters in paralysis-mediated synapse induction, ectopic expression o f agrin, a factor from motor neurons controlling neuromuscular synapse form ation, was made dependent on the administration of doxycycline in innervate d adult muscle fibers. In response to doxycycline-induced agrin secretion, adult fibers did form ectopic postsynaptic specializations, even when they were electrically active, lacked fetal AChRs, and expressed normal low leve ls of MuSK. These data demonstrate that paralysis and changes associated wi th it are not required for agrin-induced postsynapse formation. They sugges t that paralyzed muscle induces synapse formation via the release of factor s that make motor neurites contact muscle fibers and secrete agrin.