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Journal of Neuroscience, Vol 10, 894-908, Copyright © 1990 by Society for Neuroscience
In vivo visualization of the growth of pre- and postsynaptic elements of neuromuscular junctions in the mouse
RJ Balice-Gordon and JW Lichtman
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
In order to study how neuromuscular junctions grow, we have repeatedly
viewed the same junctions in mouse sternomastoid muscles at monthly
intervals from 2 weeks to 18 months of age. Motor nerve terminals were
stained with the nontoxic fluorescent dye 4-Di-2-ASP (Magrassi et al.,
1987), and postsynaptic ACh receptors were labeled with fluorescently
tagged alpha-bungarotoxin. Neuromuscular junctions grew primarily by
expansion of existing motor nerve terminal and postsynaptic receptor
regions without the addition or loss of synaptic areas. The expansion of
pre- and postsynaptic specializations was precisely matched, suggesting
that as neuromuscular junctions grow, the opposing specializations enlarge
simultaneously. Each neuromuscular junction grew in length and width at the
same rate that muscle fibers enlarged in those 2 dimensions, suggesting
that junctional growth might be a mechanical consequence of muscle fiber
growth. Repeated visualization of ACh receptors over time showed that
previously labeled receptors spread apart in the membrane occupying a
progressively larger area as muscle fibers grew. At the same time, new
receptors were intercalated throughout the enlarged postsynaptic area.
Thus, the growth of postsynaptic regions appears to be directly related to
the expansion of the muscle fiber membrane as muscle fibers grow. The
maintained alignment between growing motor nerve terminals and postsynaptic
regions suggests that nerve terminal growth may be a consequence of its
adhesion to growing postsynaptic specializations. This conclusion is
supported by the coextensive stretching of motor nerve terminals and
postsynaptic regions when muscle fibers are stretched. Thus, the growth of
motor nerve terminals is coupled to the growth of postsynaptic regions, and
the growth of the postsynaptic regions is in turn coupled to the growth of
muscle fibers. In this way, the branching pattern of neuromuscular
junctions may be stably maintained despite ongoing enlargement of synaptic
area.
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