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Article
Nature Neuroscience  6, 869 - 876 (2003)
Published online: 29 June 2003; | doi:10.1038/nn1086

New role of delta2-glutamate receptors in AMPA receptor trafficking and cerebellar function

Hirokazu Hirai1, 2, 6, Thomas Launey1, Sumiko Mikawa1, Takashi Torashima1, 2, Dai Yanagihara3, 4, Tsuyoshi Kasaura3, Akihiro Miyamoto3 & Michisuke Yuzaki2, 5

1  Laboratory for Memory & Learning, RIKEN Brain Science Institute, Saitama 351-0198, Japan.

2  Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA.

3  Laboratory for Neurophysiology, Toyohashi University of Technology, Toyohashi 441-8580, Japan.

4  CREST, Japan Science and Technology Corporation (JST), Saitama 332-0012, Japan.

5  Department of Physiology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku Tokyo 160-8582, Japan.

6  Present address: Kobe University, Graduate School of Medicine and PRESTO, Japan Science and Technology Corporation (JST), 7-5-2, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Correspondence should be addressed to Hirokazu Hirai hirai@med.kobe-u.ac.jp
Previous gene knockout studies have shown that the orphan glutamate receptor delta2 (GluRdelta2) is critically involved in synaptogenesis between parallel fibers and Purkinje cells during development. However, the precise function of GluRdelta2 and whether it is functional in the mature cerebellum remain unclear. To address these issues, we developed an antibody specific for the putative ligand-binding region of GluRdelta2, and application of this antibody to cultured Purkinje cells induced AMPA receptor endocytosis, attenuated synaptic transmission and abrogated long-term depression. Moreover, injection of this antibody into the subarachnoidal supracerebellar space of adult mice caused transient cerebellar dysfunction, such as ataxic gait and poor performance in the rotorod test. These results indicate that GluRdelta2 is involved in AMPA receptor trafficking and cerebellar function in adult mice.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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