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Journal of Neuroscience, Vol 13, 834-855, Copyright © 1993 by Society for Neuroscience
In vivo observations of pre- and postsynaptic changes during the transition from multiple to single innervation at developing neuromuscular junctions
RJ Balice-Gordon and JW Lichtman
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Synaptic rearrangements in developing muscle were studied by visualizing
individual neuromuscular junctions in the sternomastoid muscle of living
neonatal mice as they underwent the transition from multiple to single
innervation. Vital staining of ACh receptors (AChRs) with
rhodamine-conjugated alpha-bungarotoxin showed that while junctions were
still multiply innervated (usually by two motor axons), regions of the
postsynaptic membrane within each junction became depleted of receptors.
Usually, several small postsynaptic areas lost AChRs in succession. In
these areas, AChRs already in the membrane rapidly disappeared compared to
a low level of receptor turnover elsewhere in the junction. Moreover, there
was no evidence of new AChRs being inserted into these areas. Within each
postsynaptic area undergoing AChR depletion, the intensity of receptor
staining decreased gradually over 1-2 d. In some junctions, it appeared
that AChRs were migrating away from areas being depleted of receptors. The
depletion of AChRs from some sites in combination with the spreading apart
of the entire receptor-rich area due to muscle fiber growth accounts for
the transformation from plaque-like to branched receptor distributions at
developing neuromuscular junctions. Vital staining of presynaptic motor
nerve terminals at junctions whose postsynaptic AChRs were also stained
showed that motor nerve terminals were lost from the same areas that were
depleted of receptors postsynaptically. Postsynaptic areas began to be
depleted of AChRs before there was any obvious loss of membrane or
intracellular staining in the overlying nerve terminal. Only when a single
innervating axon remained at a junction did loss of motor nerve terminals
and underlying AChRs largely cease. That former synaptic areas could at
later times be identified as uninnervated regions within a junction
indicates that synapse elimination during development leaves an indelible
mark on synaptic structure. These observations suggest that the withdrawal
of a motor axon from a neuromuscular junction occurs as a consequence of
the stepwise elimination of all of its synapses with that muscle fiber.
These results also suggest that an important aspect of synaptic competition
leading to axon withdrawal is the precocious loss of AChRs beneath the
nerve terminals of the axon that will be eliminated. A similar early loss
of AChRs beneath one axon's synapses has been shown to occur during synapse
elimination in reinnervated adult muscle (Rich and Lichtman,
1989a).(ABSTRACT TRUNCATED AT 400 WORDS)
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