D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor

Wataru Kakegawa, Yurika Miyoshi, Kenji Hamase, Shinji Matsuda, Keiko Matsuda, Kazuhisa Kohda, Kyoichi Emi, Junko Motohashi, Ryuichi Konno, Kiyoshi Zaitsu, Michisuke Yuzaki

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)


D-Serine (D-Ser) is an endogenous co-agonist for NMDA receptors and regulates neurotransmission and synaptic plasticity in the forebrain. D-Ser is also found in the cerebellum during the early postnatal period. Although D-Ser binds to the δ glutamate receptor (GluD2, Grid2) in vitro, its physiological significance has remained unclear. Here we show that D-Ser serves as an endogenous ligand for GluD2 to regulate long-term depression (LTD) at synapses between parallel fibers and Purkinje cells in the immature cerebellum. D-Ser was released mainly from Bergmann glia after the burst stimulation of parallel fibers in immature, but not mature, cerebellum. D-Ser rapidly induced endocytosis of AMPA receptors and mutually occluded LTD in wild-type, but not Grid2-null, Purkinje cells. Moreover, mice expressing mutant GluD2 in which the binding site for D-Ser was disrupted showed impaired LTD and motor dyscoordination during development. These results indicate that glial D-Ser regulates synaptic plasticity and cerebellar functions by interacting with GluD2.

Original languageEnglish
Pages (from-to)603-613
Number of pages11
JournalNature Neuroscience
Issue number5
Publication statusPublished - May 2011

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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