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

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elimination has been analysed in detail, muscle fibres are initially innervated by multiple axons, then all but one are withdrawn and the ‘winner’ enlarges4,5,6.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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Correspondence to Joshua R. Sanes.

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The authors declare that they have no competing financial interests.

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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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