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Journal of Neuroscience, Vol 11, 238-255, Copyright © 1991 by Society for Neuroscience
The regulation of synaptogenesis during normal development and following activity blockade
LM Dahm and LT Landmesser
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269.
The mature neuromuscular junction is characterized by the tight spatial
colocalization of synaptic vesicles and acetylcholine receptor (AChR)
clusters. Although a large body of work exists on the interactions between
motoneurons and myotubes leading to synaptogenesis in tissue culture, how
the neuromuscular junction acquires its highly specialized structure in
vivo is not well understood, particularly during the earliest period of
synaptogenesis. In this study, the development of the neuromuscular synapse
in chick hindlimb muscles was examined and quantified by simultaneously
labeling the pre- and postsynaptic elements from the time the main nerve
trunks leave the lumbosacral plexus region to enter the developing limb (St
24) through the end of the motoneuron cell death period (St 36). Based on
these results, synaptogenesis can be divided into several distinct stages
that are intimately connected to the innervation sequence described in a
previous paper (Dahm and Landmesser, 1988). Briefly, as large nerve trunks
approach the developing muscles and the first AChR clusters are induced to
form on nearby myotubes, none of these initial receptor clusters are in
direct contact with a nerve profile. The first appearance of
nerve-contacted clusters (synapses) is coincident with the growth of large,
unbranched nerve trunks into the muscles. The next step is initiated by the
formation of small nerve side branches that grow out from the larger
intramuscular nerve trunks to bring most axons and myotubes into contact
for the first time. As side branches form, synapses appear around them, and
non-nerve-contacted receptor clusters disappear from around the main
intramuscular nerve trunks. The next step in synaptogenesis is the
restriction of synaptic vesicle antigen to sites of synaptic contact. These
early stages of synaptogenesis are also characterized by the growth of the
presynaptic terminal to match the length of the postsynaptic receptor
cluster. This study showed that AChR cluster formation during early in vivo
neuromuscular development does not require close anatomical nerve contact,
but that the presence of the nerves is necessary for AChR clusters to form.
This suggests that the nerves normally induce AChR clustering via the
release of a diffusible substance, a suggestion substantiated by the
observation that AChR clusters do not form on aneural myotubes in vivo. In
order to assess the role of synapse formation in the regulation of
motoneuron number, synaptogenesis was quantitatively examined after chronic
neuromuscular blockade, which prevents motoneuron cell death.(ABSTRACT
TRUNCATED AT 400 WORDS)
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