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Calcium‐dependent regulation of climbing fibre synapse elimination during postnatal cerebellar development
Author(s) -
Kano Masanobu,
Nakayama Hisako,
Hashimoto Kouichi,
Kitamura Kazuo,
Sakimura Kenji,
Watanabe Masahiko
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.248252
Subject(s) - cerebellum , synapse , climbing fiber , purkinje cell , neuroscience , chemistry , chromosomal translocation , biology , electrophysiology , biophysics , microbiology and biotechnology , medicine , biochemistry , gene
Functional neural circuit formation during postnatal development involves massive elimination of early‐formed redundant synapses and strengthening of necessary synaptic connections. In the cerebellum, one‐to‐one connection from a climbing fibre (CF) to a Purkinje cell (PC) is established through four distinct phases: (1) strengthening of a single CF among multiple CFs in each PC at postnatal age P3–P7 days, (2) translocation of a single strengthened CF to PC dendrites from around P9, (3) early‐phase (P7 to around P11) and (4) late‐phase (around P12–P17) elimination of weak CF synapses from PC somata. Mice with PC‐selective deletion of the P/Q‐type voltage‐dependent Ca 2+ channel (VDCC) exhibit severe defects in strengthening of single CFs, dendritic translocation of single CFs and CF elimination from P7. In contrast, mice with a mutation of a single allele for the GABA synthesizing enzyme GAD67 show selective impairment of CF elimination from P10. Electrophysiological and Ca 2+ imaging data suggest that GABA A receptor‐mediated inhibition onto PC somata from putative basket cells influences CF‐induced Ca 2+ transients and regulates elimination of redundant CF synapses from PC somata at P10–P16. Thus, regulation of Ca 2+ influx to PCs through VDCCs is crucial for the four phases of CF synapse elimination during postnatal development.