Increased and decreased activity elicits specific morphological adaptations of the neuromuscular junction

The objective of this investigation was to compare the effects of decreased vs. increased activity on the neuromuscular system. Twenty-four young adult (7 weeks old) Sprague–Dawley rats were randomly assigned to three treatment groups (N=8/group). Increased activity was achieved by treadmill running for up to 1 h/day. Decreased activity was induced by muscle unloading via the hindlimb suspension model. Control animals engaged in normal weight bearing and ambulatory activity. At the end of the 10 week intervention period, animals were killed and soleus muscles were removed, quickly frozen, and examined using cytofluorescent (neuromuscular junctions) and histochemical (myofibers) procedures. Pre-synaptic morphology was quantified by measuring nerve terminal branching, and post-synaptic assessment was conducted by staining acetylcholine receptors at the endplate. Myofiber profiles of solei were compiled by determining fiber size (cross-sectional area) and fiber type composition. Results show that exercise training significantly (P≤0.05) enhanced nerve terminal branching without modifying endplate size. In contrast, muscle unloading failed to influence nerve terminal branching, but significantly reduced endplate dimensions. Likely, the diminution of endplate size among unloaded myofibers was caused by the dramatic loss of size (∼60%) observed among those fibers. Both increased and decreased activity evoked reductions in the ratio of endplate area to length of nerve terminal branches, thus altering the pre- to post-synaptic relationship of neuromuscular junctions. In conclusion, the present data demonstrate that both increased and decreased activity significantly remodels the neuromuscular junction, but the locus (pre- vs. post-synaptic) and nature (expansion vs. reduction) of that remodeling are specific to the form of the alteration in activity.