Regional heterogeneity in the distal motor axon: three zones with distinctive intrinsic components

In this study we examined the distribution of cytoskeletal and other intrinsic axonal elements in motor nerve terminals in vivo. Components of axons were visualized with immunocytochemical staining of frozen longitudinal sections of muscle. Using these methods we compared the distribution of neurofilaments, tubulin, MAP2, actin and synaptic elements in distal regions of axons at and near neuromuscular junctions in rat muscles. Our results show that three discrete regions can be defined based on the anatomy and intrinsic components of distal axons. The preterminal axon, extending from its exit from the intramuscular nerve toward the neuromuscular junction, has a cytoskeletal composition similar to the more proximal axon with abundant staining of neurofilaments, tubulin, MAP2 and actin. The terminal arborization, a branched region of the axon extending through the endplate region, contains neurofilaments but little tubulin, actin, MAP2 or synaptic elements. Finally, the synaptic zone, demonstrated with antibodies to the synaptic vesicle protein synaptophysin, contains few cytoskeletal elements. We conclude that there is considerable regional heterogeneity in the composition of distal motor axons. The distribution of neurofilaments, other cytoskeletal elements and synaptic vesicle proteins varies among different discrete zones of terminal motor axons.