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Nat Neurosci. 2011 May;14(5):603-11. doi: 10.1038/nn.2791. Epub 2011 Apr 3.

D-serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor.

Author information

1
Department of Physiology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.

Abstract

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 δ2 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.

PMID:
21460832
DOI:
10.1038/nn.2791
[Indexed for MEDLINE]

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