The role of neuronal identity in synaptic competition


In developing mammalian muscle, axon branches of several motor neurons co-innervate the same muscle fibre. Competition among them results in the strengthening of one and the withdrawal of the rest1,2. It is not known why one particular axon branch survives or why some competitions resolve sooner than others3. Here we show that the fate of axonal branches is strictly related to the identity of the axons with which they compete. When two neurons co-innervate multiple target cells, the losing axon branches in each contest belong to the same neuron and are at nearly the same stage of withdrawal. The axonal arbor of one neuron engages in multiple sets of competitions simultaneously. Each set proceeds at a different rate and heads towards a common outcome based on the identity of the competitor. Competitive vigour at each of these sets of local competitions depends on a globally distributed resource: neurons with larger arborizations are at a competitive disadvantage when confronting neurons with smaller arborizations. An accompanying paper tests the idea that the amount of neurotransmitter released is this global resource4.

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Figure 1: Reconstructions of two competing motor units in a developing muscle.
Figure 2: Double-coloured motor units in neonatal mice.
Figure 3: Cohort of junctions co-innervated by the same two motor units are all similarly innervated.
Figure 4: The identity of neuronal competitors determines the outcome of synapse elimination.


  1. 1

    Purves, D. & Lichtman, J. W. Elimination of synapses in the developing nervous system. Science 210, 153–157 (1980)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Wong, R. O. L. & Lichtman, J. W. in Fundamental Neuroscience (ed. Squire, L. et al.) 533–553 (Academic, San Diego, 2003)

    Google Scholar 

  3. 3

    Keller-Peck, C. R. et al. Asynchronous synapse elimination in neonatal motor units: studies using GFP transgenic mice. Neuron 31, 381–394 (2001)

    CAS  Article  Google Scholar 

  4. 4

    Buffelli, M. et al. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature, this issue (2003)

  5. 5

    Lichtman, J. W. The reorganization of synaptic connexions in the rat submandibular ganglion during post-natal development. J. Physiol. (Lond.) 273, 155–177 (1977)

    CAS  Article  Google Scholar 

  6. 6

    Colman, H., Nabekura, J. & Lichtman, J. W. Alterations in synaptic strength preceding axon withdrawal. Science 275, 356–361 (1997)

    CAS  Article  Google Scholar 

  7. 7

    Chen, C. & Regehr, W. G. Developmental remodeling of the retinogeniculate synapse. Neuron 28, 955–966 (2000)

    CAS  Article  Google Scholar 

  8. 8

    Brown, M. C., Jansen, J. K. & Van Essen, D. C. Polyneural innervation of skeletal muscle in newborn rats and its elimination during maturation. J. Physiol. (Lond.) 261, 387–422 (1976)

    CAS  Article  Google Scholar 

  9. 9

    Jansen, J. K. & Fladby, T. The perinatal reorganization of the innervation of skeletal muscle in mammals. Prog. Neurobiol. 34, 39–90 (1990)

    CAS  Article  Google Scholar 

  10. 10

    Sanes, J. R. & Lichtman, J. W. Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 389–442 (1999)

    CAS  Article  Google Scholar 

  11. 11

    Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000)

    CAS  Article  Google Scholar 

  12. 12

    Press, W. H., Teukolsky, S. A., Vetterling, W. T. & Flannery, B. P. Numerical Recipes in C (Cambridge Univ. Press, 1992)

    Google Scholar 

  13. 13

    Gan, W. B. & Lichtman, J. W. Synaptic segregation at the developing neuromuscular junction. Science 282, 1508–1511 (1998)

    CAS  Article  Google Scholar 

  14. 14

    Personius, K. E. & Balice-Gordon, R. J. Activity-dependent editing of neuromuscular synaptic connections. Brain Res. Bull. 53, 513–522 (2000)

    CAS  Article  Google Scholar 

  15. 15

    Balice-Gordon, R. J. & Lichtman, J. W. Long-term synapse loss induced by focal blockade of postsynaptic receptors. Nature 372, 519–524 (1994)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Buffelli, M., Busetto, G., Cangiano, L. & Cangiano, A. Perinatal switch from synchronous to asynchronous activity of motoneurons: link with synapse elimination. Proc. Natl Acad. Sci. USA 99, 13200–13205 (2002)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Personius, K. E. & Balice-Gordon, R. J. Loss of correlated motor neuron activity during synaptic competition at developing neuromuscular synapses. Neuron 31, 395–408 (2001)

    CAS  Article  Google Scholar 

  18. 18

    Barber, M. J. & Lichtman, J. W. Activity-driven synapse elimination leads paradoxically to domination by inactive neurons. J. Neurosci. 19, 9975–9985 (1999)

    CAS  Article  Google Scholar 

  19. 19

    Walsh, M. K. & Lichtman, J. W. In vivo time lapse imaging of synaptic takeover assosciated with naturally occurring synapse elimination. Neuron 37, 1–7 (2003)

    Article  Google Scholar 

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We thank the members of our laboratory and J. R. Sanes for many useful discussions, J. Tollet for help breeding animals, J. D. Wiley for assistance in collecting initial data, and S. Turney for technical advice and developing programs for the statistical tests. We thank J. R. Sanes and G. Feng for generating the original transgenic mice. This work was supported by grants from the National Institutes of Health and the Muscular Dystrophy Association to J.W.L., and by support from the Bakewell Neuroimaging Fund.

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Correspondence to Jeff W. Lichtman.

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Kasthuri, N., Lichtman, J. The role of neuronal identity in synaptic competition. Nature 424, 426–430 (2003).

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