Effects of insulin-like growth factor I on climbing fibre synapse elimination during cerebellar development

Eur J Neurosci. 2003 Feb;17(3):545-54. doi: 10.1046/j.1460-9568.2003.02486.x.


Functional neural circuit formation includes the process by which redundant synaptic connections formed earlier during development are subsequently eliminated. We report that insulin-like growth factor I (IGF-I) is a candidate factor that influences the developmental transition from multiple to mono innervation of cerebellar Purkinje cells (PCs) by climbing fibres (CFs). Continuous local application of exogenous IGF-I to the mouse cerebellum by means of ethylene-vinyl acetate copolymer (Elvax) significantly increased the degree of multiple CF innervation, when the IGF-I containing Elvax was implanted at postnatal day 8 (P8). In contrast, the IGF-I application starting at P12 had no effect on CF innervation. Conversely, continuous local application of antisera against IGF-I and its receptor significantly decreased the degree of multiple CF innervation when the application started at P8. We found that chronic treatment of exogenous IGF-I from P8 significantly enhanced the CF-mediated excitatory postsynaptic currents (CF-EPSCs). This effect was manifest for the smaller CF-EPSCs but not for the largest CF-EPSC of the multiple-innervated PCs. Conversely, chronic application of antisera from P8 caused attenuation of the largest CF-EPSCs. Other parameters for basic synaptic functions and cerebellar morphology were largely normal after the IGF-I or antisera treatment. These results suggest that IGF-I enhances the strength of developing CF synapses and may promote their survival, whereas the shortage of IGF-I impairs the development of CF synapses and, as a result, may facilitate their elimination. Thus, IGF-I is a potentially important factor among various signalling molecules that can influence CF synapse elimination during cerebellar development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Blocking / pharmacology
  • Cerebellum / cytology*
  • Cerebellum / drug effects*
  • Cerebellum / growth & development
  • Drug Implants
  • Electrophysiology
  • Humans
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / immunology
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Fibers / drug effects*
  • Purkinje Cells / drug effects
  • Receptor, IGF Type 1 / drug effects
  • Receptor, IGF Type 1 / metabolism
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects


  • Antibodies, Blocking
  • Drug Implants
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1