Progression of age changes in mature mouse motor nerve terminals and its relation to locomotor activity

There is indirect evidence for morphologic 'turnover' of motor nerve terminals, but the consequences in terms of changing nerve terminal structure throughout mature lifetime are unknown. Therefore, quantitative morphometry of nerve terminals stained with zinc iodide-osmium was carried out in soleus and extensor digitorum longus (EDL) muscles of CBF-1 mice at various ages from 5 to 32 months. Because of previous questions as to the role of disuse in producing age changes in nerve terminal structure, locomotor activity was recorded for an average of 20 days continuously in mice spanning the same ages. The length, area, perimeter and tortuosity of nerve terminals increased either early in maturity (soleus) or progressively with age (EDL). Another prominent change, i.e. increased numbers of nerve terminal 'regions' (branches or boutons that are spatially separate or only connected by fine nerve filaments) per junction, only appeared late in life (at or after 25 months). This regionalization was characteristic of all terminals and involved a redistribution rather than an accretion of nerve terminal area. None of the morphological changes with age sufficiently account for previously reported physiologic findings in the same muscles. Locomotor activity (including peaks and troughs of daily activity and circadian rhythm) was not significantly altered over the period of mature lifetime in which nerve terminals were remodelling; therefore, disuse was not a factor in this process. However, slightly retarded and smaller age changes in soleus than in EDL nerve terminals may reflect a modifying effect of activity. It is inferred that two major processes account for morphologic alterations in nerve terminals of mature mice: changes that are simple continuations of normal development and late changes that reflect newly arising age-dependent extrinsic or intrinsic factors.