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Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition

Nature volume 424, pages 430–434 (2003)Cite this article

Abstract

Synaptic activity drives synaptic rearrangement in the vertebrate nervous system; indeed, this appears to be a main way in which experience shapes neural connectivity1,2. One rearrangement that occurs in many parts of the nervous system during early postnatal life is a competitive process called ‘synapse elimination’3,4. At the neuromuscular junction, where synapse elimination has been analysed in detail, muscle fibres are initially innervated by multiple axons, then all but one are withdrawn and the ‘winner’ enlarges4,5,6. In support of the idea that synapse elimination is activity dependent, it is slowed or speeded when total neuromuscular activity is decreased or increased, respectively4,7,8,9,10,11,12,13. However, most hypotheses about synaptic rearrangement postulate that change depends less on total activity than on the relative activity of the competitors1,2,3,4,13,14. Intuitively, it seems that the input best able to excite its postsynaptic target would be most likely to win the competition, but some theories and results make other predictions14,15,16,17,18. Here we use a genetic method to selectively inhibit neurotransmission from one of two inputs to a single target cell. We show that more powerful inputs are strongly favoured competitors during synapse elimination.

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Figure 1: Activation of gene expression in subsets of motor neurons.
Figure 2: ChAT+ axons are favoured competitors over ChAT- axons at multiply innervated neuromuscular junctions.
Figure 3: ChAT- axons fare worse when pitted against a ChAT+ axon than when pitted against another ChAT- axon.

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Acknowledgements

We thank T. Misgeld and J. Weiner for comments, and R. Lewis for assistance. This work was supported by grants from the National Institutes of Health to J.R.S. and J.W.L.

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Author notes

  1. Robert W. Burgess

    Present address: Jackson Laboratories, Bar Harbor, Maine, 04609, USA

  2. Guoping Feng

    Present address: Department of Neurobiology, Duke University Medical School, Durham, North Carolina, 27710, USA

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, St Louis, 63110, Missouri, USA

    Mario Buffelli, Robert W. Burgess, Guoping Feng, Jeff W. Lichtman & Joshua R. Sanes

  2. Dipartimento di Scienze Neurologiche e della Visione, Università degli Studi di Verona, Via dell' Artigliere 8, 37129, Verona, Italy

    Mario Buffelli

  3. Sunnybrook and Women's College Health Science Centre, 2075 Bayview, Toronto, Ontario, MN4 3M5, Canada

    Corrinne G. Lobe

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Correspondence to Joshua R. Sanes.

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Buffelli, M., Burgess, R., Feng, G. et al. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424, 430–434 (2003). https://doi.org/10.1038/nature01844

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