The role of neuronal identity in synaptic competition

Abstract

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.

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Acknowledgements

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). https://doi.org/10.1038/nature01836

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