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Volume 17, Number 24,
Issue of December 15, 1997
pp. 9613-9623
Impaired Parallel Fiber Purkinje Cell Synapse Stabilization
during Cerebellar Development of Mutant Mice Lacking the Glutamate
Receptor  2 Subunit
Received July 8, 1997; revised Sept. 22, 1997; accepted Sept. 26, 1997.
Hideo Kurihara1, 2,
Kouichi Hashimoto3, 4,
Masanobu Kano3, 4,
Chitoshi Takayama1,
Kenji Sakimura5,
Masayoshi Mishina,
Yoshiro Inoue1, and
Masahiko Watanabe1
Departments of 1 Anatomy and
2 Otolaryngology, Hokkaido University School of Medicine,
Sapporo 060, Japan, 3 Department of Physiology, Jichi
Medical School, Minamikawachi-machi, Tochigi-ken 329-04, Japan,
4 Laboratory for Neuronal Signal Transduction, Frontier
Research Program, RIKEN, Wako-shi, Saitama 351-01, Japan,
5 Department of Cellular Neurobiology, Brain Research
Institute, Niigata University, Niigata 951, Japan, and Department of
Molecular Neurobiology and Pharmacology, School of Medicine, University
of Tokyo, Tokyo 113, Japan
The glutamate receptor  2 subunit (GluR2) 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 GluR2 gene leads to a significant reduction of PF PC synapses. To
address its role in the synaptogenesis, the morphology and electrophysiology of PFPC synapses were comparatively examined in
developing GluR2 mutant and wild-type cerebella. PCs in GluR2 mutant mice were normally produced, migrated, and formed spines, as did
those in wild-type 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 GluR2 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.
Key words:
glutamate receptor 2 subunit;
gene knock-out;
cerebellum;
Purkinje cell;
parallel fiber synapse;
synapse formation;
development;
mouse
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