Related Experiment Video
Updated: Jun 3, 2026

Assessment of Long-term Depression Induction in Adult Cerebellar Slices
Published on: October 16, 2019
D-serine regulates cerebellar LTD and motor coordination through the δ2 glutamate receptor
Wataru Kakegawa1, Yurika Miyoshi, Kenji Hamase
1Department 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.
More Related Videos
Related Concept Videos
Long-term Depression
Calcium Ion Concentration Mechanism
If over time, all...
Long-term Depression
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Major Somatic Sensory Pathways
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
Diencephalon: Thalamus and Information Relay

