Synaptic competition for neurotrophins

The development of connections between neurons and their target cells often involves an initial stage of superinnervation followed by elimination of axons. In some cases, elimination continues until the target is innervated by just a single axon (e.g., in the neuromuscular junction), whereas in many other cases various innervating axons remain.

Competition among axons for target-derived neurotrophins (survival promoting factors) is thought to play a key role in axon elimination. Although the notion of competition is widely used, there is little understanding of the nature of the competitive process and the underlying mechanisms.

Our model predicts that for competition to arise, neurotrophins need to upregulate the number of their own receptors (Van Ooyen and Willshaw, 1999). This prediction has recently been confirmed experimentally in a study showing that nerve growth factor (NGF) promotes the expression of its own receptor TrkA and that perturbation of this feedback disrupts the dynamics of synaptic competition (Deppmann et al., 2008).

• Competition in neurite outgrowth and the development of nerve connections
  Van Ooyen, A. (2005). In: Van Pelt, J. Kamermans, M., Levelt, C. N., Van Ooyen, A., Ramakers, G. J. A., and Roelfsema, P. R., eds. Development, Dynamics and Pathology of Neuronal Networks: From Molecules to Functional Circuits, Progress in Brain Research 147. Amsterdam: Elsevier, pp. 81-99.
  [Abstract] [Full text: PDF]

• Competition in the development of nerve connections
  Van Ooyen, A., and Ribchester, R. R. (2003). In: Van Ooyen, A., ed. Modeling Neural Development. Cambridge, MA: MIT Press, pp. 183-211.
  [Abstract] [Full text: PDF]

• Competition in neuronal morphogenesis and the development of nerve connections
  Van Ooyen, A., and Van Pelt, J. (2002). In: Ascoli, G., ed. Computational Neuroanatomy: Principles and Methods. Totowa, NJ: Humana Press Inc., pp. 219-244.
  [Abstract] [Full text: PDF]

• Competition in the development of nerve connections: a review of models
  Van Ooyen, A. (2002) (invited review). Network: Computation in Neural Systems 12: R1-R47.
  [Abstract] [Full text: PDF]

• Development of nerve connections under the control of neurotrophic factors: parallels with consumer-resource systems in population biology
  Van Ooyen, A., and Willshaw, D. J. (2000). J. Theor. Biol. 206: 195-210.
  [Abstract] [Full text: PDF]

• Influence of dendritic morphology on axonal competition
  Van Ooyen, A., Willshaw, D. J., and Ramakers, G. J. A. (2000). Neurocomputing 32-33: 255-260.
  [Abstract] [Full text: PDF]

• Poly-and mononeuronal innervation in a model for the development of neuromuscular connections
  Van Ooyen, A., and Willshaw, D. J. (1999). J. Theor. Biol. 196: 495-511.
  [Abstract] [Full text: PDF]

• Influence of dendritic morphology on axonal competition
  Van Ooyen, A., and Willshaw, D. J. (1999). In: Artificial Neural Networks - ICANN 1999, 9th International Conference on Artificial Neural Networks, Edinburgh, UK, September 1999, pp. 1000-1005.
  [Abstract] [Full text: PDF]

• Competition for neurotrophic factor in the development of nerve connections
  Van Ooyen, A., and Willshaw, D. J. (1999). Proc. R. Soc. Lond. B 266: 883-892.
  [Abstract] [Full text: PDF]

• Competition amongst neurons for neurotrophins
  Van Ooyen, A., and Willshaw, D. J. (1997). In: Gerstner, W., Germond, A., Hasler, M., Nicoud, J.-D., eds. Artificial Neural Networks - ICANN97, 7th International Conference on Artificial Neural Networks, Lausanne, Switzerland. Berlin: Springer, pp. 139-144.
  [Abstract] [Full text: PDF]