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Effects of insulin‐like growth factor I on climbing fibre synapse elimination during cerebellar development
Author(s) -
Kakizawa Sho,
Yamada Kazuyuki,
Iino Masamitsu,
Watanabe Masahiko,
Kano Masanobu
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02486.x
Subject(s) - cerebellum , synapse , excitatory postsynaptic potential , climbing fiber , insulin like growth factor , neuroscience , postsynaptic potential , medicine , biology , endocrinology , growth factor , chemistry , receptor , purkinje cell , inhibitory postsynaptic potential , biochemistry
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.