PT  - JOURNAL ARTICLE
AU  - Yoshiaki Ohtani
AU  - Mariko Miyata
AU  - Kouichi Hashimoto
AU  - Toshihide Tabata
AU  - Yasushi Kishimoto
AU  - Masahiro Fukaya
AU  - Daisuke Kase
AU  - Hidetoshi Kassai
AU  - Kazuki Nakao
AU  - Tatsumi Hirata
AU  - Masahiko Watanabe
AU  - Masanobu Kano
AU  - Atsu Aiba
TI  - The Synaptic Targeting of mGluR1 by Its Carboxyl-Terminal Domain Is Crucial for Cerebellar Function
AID  - 10.1523/JNEUROSCI.3542-13.2014
DP  - 2014 Feb 12
TA  - The Journal of Neuroscience
PG  - 2702--2712
VI  - 34
IP  - 7
4099  - http://www.jneurosci.org/content/34/7/2702.short
4100  - http://www.jneurosci.org/content/34/7/2702.full
SO  - J. Neurosci.2014 Feb 12; 34
AB  - The metabotropic glutamate receptor subtype 1 (mGluR1, Grm1) in cerebellar Purkinje cells (PCs) is essential for motor coordination and motor learning. At the synaptic level, mGluR1 has a critical role in long-term synaptic depression (LTD) at parallel fiber (PF)-PC synapses, and in developmental elimination of climbing fiber (CF)-PC synapses. mGluR1a, a predominant splice variant in PCs, has a long carboxyl (C)-terminal domain that interacts with Homer scaffolding proteins. Cerebellar roles of the C-terminal domain at both synaptic and behavior levels remain poorly understood. To address this question, we introduced a short variant, mGluR1b, which lacks this domain into PCs of mGluR1-knock-out (KO) mice (mGluR1b-rescue mice). In mGluR1b-rescue mice, mGluR1b showed dispersed perisynaptic distribution in PC spines. Importantly, mGluR1b-rescue mice exhibited impairments in inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release, CF synapse elimination, LTD induction, and delay eyeblink conditioning: they showed normal transient receptor potential canonical (TRPC) currents and normal motor coordination. In contrast, PC-specific rescue of mGluR1a restored all cerebellar defects of mGluR1-KO mice. We conclude that the long C-terminal domain of mGluR1a is required for the proper perisynaptic targeting of mGluR1, IP3R-mediated Ca2+ release, CF synapse elimination, LTD, and motor learning, but not for TRPC currents and motor coordination.