| First Author | Kakegawa W | Year | 2011 |
| Journal | Nat Neurosci | Volume | 14 |
| Issue | 5 | Pages | 603-11 |
| PubMed ID | 21460832 | Mgi Jnum | J:172289 |
| Mgi Id | MGI:5006881 | Doi | 10.1038/nn.2791 |
| Citation | Kakegawa W, et al. (2011) D-Serine regulates cerebellar LTD and motor coordination through the delta2 glutamate receptor. Nat Neurosci 14(5):603-11 |
| abstractText | 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 delta2 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. |
