Journal of Neuroscience, Vol 10, 2660-2671, Copyright © 1990 by Society for Neuroscience
Neuromuscular junctions shrink and expand as muscle fiber size is manipulated: in vivo observations in the androgen-sensitive bulbocavernosus muscle of mice
RJ Balice-Gordon, SM Breedlove, S Bernstein and JW Lichtman
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Neuromuscular synapses in an androgen-sensitive muscle of sexually mature
male mice were repeatedly observed over several-month intervals in normal
animals and in animals in which testosterone levels were manipulated. In
normal bulbocavernosus muscles, pre- and postsynaptic regions of
neuromuscular junctions enlarge as muscle fibers grow. After castration,
junctional area decreased in parallel with muscle fiber atrophy. When
testosterone was resupplied to castrated animals, junctions that previously
decreased in size then enlarged in parallel with muscle fiber hypertrophy.
Surprisingly, these size changes occurred without loss or addition of motor
nerve terminal branches or acetylcholine (ACh) receptor regions. Rather,
each nerve terminal branch and underlying receptor region became smaller
following castration and reenlarged following testosterone treatment.
Several lines of evidence argued that the size changes observed after
castration and testosterone treatment were secondary to shrinkage and
stretching of the postsynaptic muscle fiber membrane. Following castration,
the spaces between synaptic regions decreased in size at the same time and
to a similar extent as the regions themselves. Following testosterone
replacement, the spaces between synaptic regions expanded and each existing
ACh receptor region enlarged. Ultrastructural analysis showed that there
was no loss or addition of postsynaptic secondary junctional folds in the
muscle fiber membrane (where ACh receptors are located) as junctions shrank
and expanded. Rather, folds became more densely packed as muscle fibers
atrophied following castration and less densely packed as muscle fibers
hypertrophied following testosterone replacement. From these studies of the
bulbocavernosus muscle, as from our previous studies of the sternomastoid
muscle, we conclude that neuromuscular junction size is directly coupled to
muscle fiber size. Androgens modulate muscle fiber volume directly, leading
to a change in the surface area of the muscle fiber membrane, which in turn
causes the postsynaptic specializations to shrink or expand. The
concomitant shrinkage and stretching of motor nerve terminals that we
observed can only be accounted for by their adhesion to postsynaptic
specializations that are also changing size. Thus adhesion, rather than an
interchange of diffusible factors, trophic or otherwise, is likely to be
the primary determinant of coordinated pre- and postsynaptic enlargement in
growing mammalian skeletal muscles.
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