The Journal of Neuroscience, July 1, 1998, 18(13):4953-4965
Axon Withdrawal during Synapse Elimination at the Neuromuscular
Junction Is Accompanied by Disassembly of the Postsynaptic
Specialization and Withdrawal of Schwann Cell Processes
Susan M.
Culican,
Carla C.
Nelson, and
Jeff W.
Lichtman
Department of Anatomy and Neurobiology, Washington University
School of Medicine, St Louis, MO 63110
Nerve terminal withdrawal is accompanied by a loss of acetylcholine
receptors (AChRs) at corresponding postsynaptic sites during the
process of synapse elimination at developing () and reinnervated adult ()
neuromuscular junctions. Aside from AChR and nerve terminal loss,
however, the molecular and cellular alterations that occur at sites of
elimination are unknown. To gain a better understanding of the cascade
of events that leads to the disassembly of synaptic sites during the
synapse elimination process, we surveyed the distribution of molecular
elements of the postsynaptic specialization, the basal lamina, and
supporting Schwann cells during the process of synapse elimination that
occurs after reinnervation. In addition, quantitative techniques were
used to determine the temporal order of disappearance of molecules that
were lost relative to the loss of postsynaptic AChRs. We found that the
dismantling of the postsynaptic specialization was inhomogeneous, with
evidence of rapid dissolution of some aspects of the postsynaptic
apparatus and slower loss of others. We also observed a loss of Schwann
cell processes from sites of synapse elimination, with a time course
similar to that seen for nerve terminal retraction. In contrast, all of
the extracellular markers that we examined were lost slowly from sites
of synapse loss. We therefore conclude that the synapse elimination
process is synapse-wide, removing not only nerve terminals but also
Schwann cells and many aspects of the postsynaptic apparatus. The
disassembly occurs in a stereotyped sequence with some synaptic
elements appearing much more stable than others.
Key words:
neuromuscular junction; synapse elimination; AChR; postsynaptic specialization; Schwann cell; synaptic competition
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