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

Nature. 2003 Jul 24;424(6947):430-4. doi: 10.1038/nature01844.


Synaptic activity drives synaptic rearrangement in the vertebrate nervous system; indeed, this appears to be a main way in which experience shapes neural connectivity. One rearrangement that occurs in many parts of the nervous system during early postnatal life is a competitive process called 'synapse elimination'. 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elimination has been analysed in detail, muscle fibres are initially innervated by multiple axons, then all but one are withdrawn and the 'winner' enlarges. In support of the idea that synapse elimination is activity dependent, it is slowed or speeded when total neuromuscular activity is decreased or increased, respectively. However, most hypotheses about synaptic rearrangement postulate that change depends less on total activity than on the relative activity of the competitors. 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 predictions. 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology
  • Choline O-Acetyltransferase / genetics
  • Choline O-Acetyltransferase / metabolism
  • Gene Deletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Neurological*
  • Motor Neurons / metabolism
  • Muscle, Skeletal / innervation*
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / physiology
  • Neuronal Plasticity
  • Synapses / genetics
  • Synapses / physiology*
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Transgenes / genetics


  • Choline O-Acetyltransferase