Effects of insulin-like growth factor I on climbing fibre synapse elimination during cerebellar development.
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.
Kakizawa
Sho
S
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Japan.
Yamada
Kazuyuki
K
Iino
Masamitsu
M
Watanabe
Masahiko
M
Kano
Masanobu
M
D000818:Animals; D000831:Animals, Newborn; D019138:Antibodies, Blocking / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D004343:Drug Implants; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000187:drug effects*; D011689:Purkinje Cells / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D019138:Antibodies, Blocking; D004343:Drug Implants; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1