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Letters to Nature
Nature 424, 430-434 (24 July 2003) | doi:10.1038/nature01844; Received 5 February 2003; Accepted 2 June 2003
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Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition
Mario Buffelli1,2, Robert W. Burgess1,3, Guoping Feng1,3, Corrinne G. Lobe4, Jeff W. Lichtman1 & Joshua R. Sanes1
- Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, St Louis, Missouri 63110, USA
- Dipartimento di Scienze Neurologiche e della Visione, Università degli Studi di Verona, Via dell' Artigliere 8, 37129 Verona, Italy
- Sunnybrook and Women's College Health Science Centre, 2075 Bayview, Toronto, Ontario MN4 3M5, Canada
- Present addresses: Jackson Laboratories, Bar Harbor, Maine 04609, USA (R.W.B.); Department of Neurobiology, Duke University Medical School, Durham, North Carolina 27710, USA (G.F.).
Correspondence to: Joshua R. Sanes1 Correspondence and requests for materials should be addressed to J.R.S. (Email: sanesj@pcg.wustl.edu).
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elimination has been analysed in detail, muscle fibres are initially innervated by multiple axons, then all but one are withdrawn and the 'winner' enlarges4, 5, 6.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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