Scanning and light microscopic study of age changes at a neuromuscular junction in the mouse.

Abstract

From previous work, it appears that synaptic transmission is well preserved at aging mouse neuromuscular junctions despite profound ultrastructural changes. Scanning and light microscopy have been used to determine whether expansion or sprouting of nerve terminals or postsynaptic reorganization play a role in this apparent compensatory mechanism. The number and length of nerve terminal branches in the extensor digitorum longus of young (7 months) and old (29 months) mice were studied with a combined silver-cholinesterase method. In aged animals, there were increases in nerve terminal length and number of intrasynaptic branches, with no change in muscle fibre diameter or numbers of axons entering the junction. Neither collateral sprouting nor collateral innervation, hallmarks of partial denervation, were present. Motor endplates visualized by scanning electron microscopy appeared as slightly elevated, elliptical plateaux ('raised areas') with smooth surfaces into which the synaptic clefts were etched. In the aged endplates more than in young endplates, the primary clefts were often interrupted by narrow short outpouchings approximately perpendicular to the long axis of the primary cleft. In addition, oval primary cleft islets were more frequent and there was increased randomness and branching of secondary clefts. Both light and scanning microscopy gave concordant quantitative evidence that nerve terminals and the underlying postsynaptic cleft are longer and more branched in aged mice. The increased length of synaptic nerve terminal approximately balances the loss of girth previously reported leaving nerve terminal volume unchanged. The observed expansion of the synaptic area in the aged neuromuscular junction may be compensatory, preserving neuromuscular function. The data also point to plasticity of adult neuromuscular synaptic structure.