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Competition at silent synapses in reinnervated skeletal muscle

Abstract

Synaptic connections are made and broken in an activity-dependent manner in diverse regions of the nervous system. However, whether activity is strictly necessary for synapse elimination has not been resolved directly. Here we report that synaptic terminals occupying motor endplates made electrically silent by tetrodotoxin and α-bungarotoxin block were frequently displaced by regenerating axons that were also both inactive and synaptically ineffective. Thus, neither evoked nor spontaneous activation of acetylcholine receptors is required for competitive reoccupation of neuromuscular synaptic sites by regenerating motor axons.

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Figure 1: Experimental design.
Figure 2: Neuromuscular junctions in paralyzed muscles stained with vital styryl dyes.
Figure 3: Motor endplates in paralyzed muscles became mainly or exclusively reinnervated by inactive axons.
Figure 4: Control experiments showing that almost all muscle fibers were occupied by LPN terminals or their sprouts before the return of regenerating SN axons.
Figure 5: Control experiments confirming the effectiveness of the chronic neuromuscular block.

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Acknowledgements

This work was supported by grants from the Medical Research Council, Action Research, the Wellcome Trust, the Royal Society and the Stanley Davidson Fund of the University of Edinburgh. We thank D. Thomson for technical assistance, T. Gillingwater for assistance with blind assays of endplate occupancy and help with some of the immunocytochemisty and R.G.M. Morris and C.R. Slater for discussions and comments on the manuscript.

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Correspondence to Richard R. Ribchester.

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Costanzo, E., Barry, J. & Ribchester, R. Competition at silent synapses in reinnervated skeletal muscle. Nat Neurosci 3, 694–700 (2000). https://doi.org/10.1038/76649

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