AXON WITHDRAWAL DURING SYNAPSE ELIMINATION AT THE NEUROMUSCULAR-JUNCTION IS ACCOMPANIED BY DISASSEMBLY OF THE POSTSYNAPTIC SPECIALIZATION AND WITHDRAWAL OF SCHWANN-CELL PROCESSES

Nerve terminal withdrawal is accompanied by a loss of acetylcholine re ceptors (AChRs) at corresponding postsynaptic sites during the process of synapse elimination at developing (Balice-Gordon and Lichtman, 199 3) and reinnervated adult (Rich and Lichtman, 1989a) neuromuscular jun ctions. Aside from AChR and nerve terminal loss, however, the molecula r and cellular alterations that occur at sites of elimination are unkn own. To gain a better understanding of the cascade of events that lead s to the disassembly of synaptic sites during the synapse elimination process, we surveyed the distribution of molecular elements of the pos tsynaptic specialization, the basal lamina, and supporting Schwann cel ls during the process of synapse elimination that occurs after reinner vation. In addition, quantitative techniques were used to determine th e temporal order of disappearance of molecules that were lost relative to the loss of postsynaptic AChRs. We found that the dismantling of t he postsynaptic specialization was inhomogeneous, with evidence of rap id dissolution of some aspects of the postsynaptic apparatus and slowe r loss of others. We also observed a loss of Schwann cell processes fr om sites of synapse elimination, with a time course similar to that se en for nerve terminal retraction. In contrast, all of the extracellula r markers that we examined were lost slowly from sites of synapse loss . We therefore conclude that the synapse elimination process is synaps e-wide, removing not only nerve terminals but also Schwann cells and m any aspects of the postsynaptic apparatus. The disassembly occurs in a stereotyped sequence with some synaptic elements appearing much more stable than others.