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Competition at silent synapses in reinnervated skeletal muscle

Nature Neuroscience volume 3, pages 694700 (2000) | Download Citation

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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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References

  1. 1.

    , & Synapse elimination in the central nervous system: functional significance and cellular mechanisms. Rev. Neurosci. 7, 85–101 (1996).

  2. 2.

    Dynamics of nerve-muscle interaction in developing and mature neuromuscular junctions. Physiol. Rev. 75, 789–834 (1995).

  3. 3.

    Neural Activity and the Growth of the Brain (Cambridge Univ. Press, Cambridge, UK, 1994).

  4. 4.

    , & The role of visual experience in the development of columns in cat visual cortex. Science 279, 566–570 (1998).

  5. 5.

    & Development of ocular dominance columns in the absence of retinal input. Nat. Neurosci. 2, 1125–1130 (1999).

  6. 6.

    , & Influence of experience on orientation maps in cat visual cortex. Nat. Neurosci. 2, 727–732 (1999).

  7. 7.

    & Synapse specificity of long-term potentiation breaks down at short distances. Nature 388, 279–284 (1997).

  8. 8.

    , & Propagation of activity-dependent synaptic depression in simple neural networks. Nature 388, 439–448 (1997).

  9. 9.

    & Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 389–442 (1999).

  10. 10.

    , & Polyneuronal innervation in newborn rats and its elimination during maturation. J. Physiol. (Lond.) 261, 387–422 (1976).

  11. 11.

    Activity-dependent and activity-independent synaptic interactions during reinnervation of partially denervated rat muscle. J. Physiol. (Lond.) 401, 53–75 (1988).

  12. 12.

    & Persistent polyneuronal innervation in partially denervated rat muscle after reinnervation and recovery from prolonged nerve-conduction block. J. Neurosci. 15, 6327–6339 (1995).

  13. 13.

    & Motor unit size and synaptic competition in rat lumbrical muscles reinnervated by active and inactive motor axons. J. Physiol. (Lond.) 344, 89–111 (1983).

  14. 14.

    & Repression of inactive motor-nerve terminals in partially denervated rat muscle after regeneration of active motor axons. J. Physiol. (Lond.) 347, 497–511 (1984).

  15. 15.

    & Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature 372, 519–524 (1994).

  16. 16.

    , & Short-term and long-term effects of paralysis on the motor innervation of 2 different neonatal mouse muscles. J. Physiol. (Lond.) 329, 439–450 (1982).

  17. 17.

    , & Differential loss of neuromuscular connections according to activity level and spinal position of neonatal rabbit soleus motor neurons. J. Neurosci. 9, 1806–1824 (1989).

  18. 18.

    Coexistence and elimination of convergent motor-nerve terminals in reinnervated and paralyzed adult rat skeletal muscle. J. Physiol. (Lond.) 466, 421–441 (1993).

  19. 19.

    , & The size of motor units during post-natal development of rat lumbrical muscle. J. Physiol. (Lond.) 297, 463–478 (1979).

  20. 20.

    , & Activity-dependent fluorescent staining and destaining of living vertebrate motor nerve terminals. J. Neurosci. 12, 363–375 (1992).

  21. 21.

    & Nonquantal release of acetylcholine affects polyneuronal innervation on developing rat muscle fibers. Eur. J. Neurosci. 5, 1677–1683 (1993).

  22. 22.

    & Effect of reinnervation on the degradation rate of junctional acetylcholine receptors synthesized in denervated skeletal muscles. J. Neurosci. 10, 3905–3915 (1990).

  23. 23.

    , & Motor nerve sprouting. Annu. Rev. Neurosci. 4, 17–42 (1981).

  24. 24.

    , & Schwann cells induce and guide sprouting and reinnervation of neuromuscular junctions. Trends Neurosci. 19, 280–285 (1996).

  25. 25.

    & Membrane properties underlying spontaneous activity of denervated muscle fibres. J. Physiol. (Lond.) 239, 125–153 (1974).

  26. 26.

    & In vivo visualization of pre- and postsynaptic changes during synapse elimination in reinnervated mouse muscle. J. Neurosci. 9, 1781–1805 (1989).

  27. 27.

    & The formation of terminal fields in the absence of competitive interactions among primary motoneurons in the zebrafish. J. Neurosci. 10, 3947–3959 (1990).

  28. 28.

    & Spatial versus consumptive competition at polyneuronally innervated neuromuscular junctions. Exp. Physiol. 79, 465–494 (1994).

  29. 29.

    Competition (Chapman & Hall, London, New York, 1989).

  30. 30.

    & Competition for neurotrophic factor in the development of nerve connections. Proc. R. Soc. Lond. B 266, 883–892 (1999).

  31. 31.

    , , & Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science 279, 1725–1729 (1998).

  32. 32.

    , , & Enhancement of spontaneous transmitter release at neonatal mouse neuromuscular junctions by the glial cell line-derived neurotrophic factor (GDNF). J. Physiol. (Lond.) 512, 635–641 (1998).

  33. 33.

    , , , & A molecular mechanism for synapse elimination: novel inhibition of locally generated thrombin delays synapse loss in neonatal mouse muscle. Dev. Biol. 179, 447–457 (1996).

  34. 34.

    & Nip and tuck at the neuromuscular junction: a role for proteases in developmental synapse elimination. Bioessays 19, 271–275 (1997).

  35. 35.

    , , , & Regulation of dense core release from neuroendocrine cells revealed by imaging single exocytic events. Nat. Neurosci. 2, 440–446 (1999).

  36. 36.

    & Are neurotrophins synaptotrophins. Mol. Cell. Neurosci. 7, 433–442 (1996).

  37. 37.

    , & Co-regulation of synaptic efficacy at stable polyneuronally innervated neuromuscular junctions in reinnervated rat muscle. J. Physiol. (Lond.) 521, 365–374 (1999).

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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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  1. Department of Neuroscience, University of Edinburgh Medical School, Edinburgh EH8 9LE, UK

    • Ellen M. Costanzo
    • , Jacqueline A. Barry
    •  & Richard R. Ribchester

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Correspondence to Richard R. Ribchester.

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https://doi.org/10.1038/76649

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