Inactivity-induced remodeling of neuromuscular junctions in rat diaphragmatic muscle

We hypothesized that inactivity-induced remodeling of neuromuscular junctions (NMJs) depends on fiber type and the match between muscle fiber and motoneuron (MN) activities. Two inactivity models were studied in rat diaphragmatic muscle: spinal hemisection at C2 (SH), where both diaphragmatic muscle fibers and phrenic MNs were inactive, and tetrodotoxin (TTX) nerve blockade, where only muscle fibers were inactive. After 2 weeks of inactivity, there was increased number of pre- and postsynaptic branches (fragmentation) of NMJs at type IIx/b fibers in both models. In addition, planar NMJ areas at type IIx/b fibers in the SH model were enlarged. In contrast, NMJs at type I and IIa fibers were unaffected in both SH and TTX models. Functionally, neuromuscular transmission in diaphragmatic muscle fibers improved in the SH model, but worsened in the TTX model, compared to controls. These results suggest that NMJ remodeling depends on the level of MN activity. The relative preservation of NMJs at type I and IIa fibers suggests a potential for recovery from diaphragmatic paralysis in the clinical setting, at least for respiratory behaviors.