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 journalArticle

91 Citations (Scopus)

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 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
Volume14
Issue number5
DOIs
Publication statusPublished - May 1 2011

Fingerprint

Glutamate Receptors
Cerebellum
Serine
Neuronal Plasticity
Purkinje Cells
Neuroglia
Null Lymphocytes
AMPA Receptors
Ataxia
Prosencephalon
Endocytosis
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Synapses
Binding Sites
Ligands

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Kakegawa, W., Miyoshi, Y., Hamase, K., Matsuda, S., Matsuda, K., Kohda, K., ... Yuzaki, M. (2011). D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor. Nature Neuroscience, 14(5), 603-613. https://doi.org/10.1038/nn.2791

D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor. / Kakegawa, Wataru; Miyoshi, Yurika; Hamase, Kenji; Matsuda, Shinji; Matsuda, Keiko; Kohda, Kazuhisa; Emi, Kyoichi; Motohashi, Junko; Konno, Ryuichi; Zaitsu, Kiyoshi; Yuzaki, Michisuke.

In: Nature Neuroscience, Vol. 14, No. 5, 01.05.2011, p. 603-613.

Research output: Contribution to journalArticle

Kakegawa, W, Miyoshi, Y, Hamase, K, Matsuda, S, Matsuda, K, Kohda, K, Emi, K, Motohashi, J, Konno, R, Zaitsu, K & Yuzaki, M 2011, 'D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor', Nature Neuroscience, vol. 14, no. 5, pp. 603-613. https://doi.org/10.1038/nn.2791
Kakegawa, Wataru ; Miyoshi, Yurika ; Hamase, Kenji ; Matsuda, Shinji ; Matsuda, Keiko ; Kohda, Kazuhisa ; Emi, Kyoichi ; Motohashi, Junko ; Konno, Ryuichi ; Zaitsu, Kiyoshi ; Yuzaki, Michisuke. / D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor. In: Nature Neuroscience. 2011 ; Vol. 14, No. 5. pp. 603-613.
@article{6404ea56ad5f42b2b43a0a7349606ea5,
title = "D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor",
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 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.",
author = "Wataru Kakegawa and Yurika Miyoshi and Kenji Hamase and Shinji Matsuda and Keiko Matsuda and Kazuhisa Kohda and Kyoichi Emi and Junko Motohashi and Ryuichi Konno and Kiyoshi Zaitsu and Michisuke Yuzaki",
year = "2011",
month = "5",
day = "1",
doi = "10.1038/nn.2791",
language = "English",
volume = "14",
pages = "603--613",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - D-Serine regulates cerebellar LTD and motor coordination through the δ glutamate receptor

AU - Kakegawa, Wataru

AU - Miyoshi, Yurika

AU - Hamase, Kenji

AU - Matsuda, Shinji

AU - Matsuda, Keiko

AU - Kohda, Kazuhisa

AU - Emi, Kyoichi

AU - Motohashi, Junko

AU - Konno, Ryuichi

AU - Zaitsu, Kiyoshi

AU - Yuzaki, Michisuke

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79955464527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955464527&partnerID=8YFLogxK

U2 - 10.1038/nn.2791

DO - 10.1038/nn.2791

M3 - Article

VL - 14

SP - 603

EP - 613

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 5

ER -