Impaired Parallel Fiber→Purkinje Cell Synapse Stabilization during Cerebellar Development of Mutant Mice Lacking the Glutamate Receptor δ2 Subunit

Hideo Kurihara, Kouichi Hashimoto, Masanobu Kano, Chitoshi Takayama, Kenji Sakimura, Masayoshi Mishina, Yoshiro Inoue, Masahiko Watanabe
1997 Journal of Neuroscience  
The glutamate receptor ␦2 subunit (GluR␦2) is specifically expressed in cerebellar Purkinje cells (PCs) from early developmental stages and is selectively localized at dendritic spines forming synapses with parallel fibers (PFs). Targeted disruption of the GluR␦2 gene leads to a significant reduction of PF3PC synapses. To address its role in the synaptogenesis, the morphology and electrophysiology of PF3PC synapses were comparatively examined in developing GluR␦2 mutant and wildtype cerebella.
more » ... Cs in GluR␦2 mutant mice were normally produced, migrated, and formed spines, as did those in wildtype mice. At the end of the first postnatal week, 74-78% of PC spines in both mice formed immature synapses, which were characterized by small synaptic contact, few synaptic vesicles, and incomplete surrounding by astroglial processes, eliciting little electrophysiological response. During the second and third postnatal weeks when spines and terminals are actively generated, the percentage of PC spines forming synapses attained 98-99% in wild type but remained as low as 55-60% in mutants, and the rest were unattached to any nerve terminals. As a result, the number of PF synapses per single-mutant PCs was reduced to nearly a half-level of wild-type PCs. Parallelly, PF stimulation less effectively elicited EPSCs in mutant PCs than in wild-type PCs during and after the second postnatal week. These results suggest that the GluR␦2 is involved in the stabilization and strengthening of synaptic connectivity between PFs and PCs, leading to the association of all PC spines with PF terminals to form functionally mature synapses.
doi:10.1523/jneurosci.17-24-09613.1997 pmid:9391016 fatcat:znly6mlb7rdpzprx53wlcpyl3m