d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor
Jean-Pierre Mothet,Angèle T. Parent,Angèle T. Parent,Herman Wolosker,Roscoe O. Brady,David J. Linden,Christopher D. Ferris,Michael A. Rogawski,Solomon H. Snyder +8 more
Reads0
Chats0
TLDR
D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses and greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMda receptor- mediated calcium flux.Abstract:
Functional activity of N-methyl-d-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although d-serine is a more potent agonist. Localizations of d-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of d-serine with d-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch–clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied d-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, d-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.read more
Citations
More filters
Journal ArticleDOI
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Stephen F. Traynelis,Lonnie P. Wollmuth,Chris J. McBain,Frank S. Menniti,Katie M. Vance,Kevin K. Ogden,Kasper B. Hansen,Hongjie Yuan,Scott J. Myers,Raymond Dingledine +9 more
TL;DR: This review discusses International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Journal ArticleDOI
Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence.
TL;DR: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry.
Journal ArticleDOI
GLIA: listening and talking to the synapse.
TL;DR: It is no longer appropriate to consider solely neuron–neuron connections; it is also necessary to develop a view of the intricate web of active connections among glial cells, and between glia and neurons.
Journal ArticleDOI
Astrocyte Control of Synaptic Transmission and Neurovascular Coupling
TL;DR: The application of subcellular imaging of Ca2+ signaling to astrocytes now provides functional data to support this structural notion that both excitatory and inhibitory signals provided by the same glial cell act in concert to regulate neuronal function.
Journal ArticleDOI
Long-term potentiation depends on release of d -serine from astrocytes
Christian Henneberger,Thomas Papouin,Thomas Papouin,Stéphane H. R. Oliet,Stéphane H. R. Oliet,Dmitri A. Rusakov +5 more
TL;DR: It is demonstrated that Ca2+-dependent release of d-serine from an astrocyte controls NMDAR-dependent plasticity in many thousands of excitatory synapses nearby.
References
More filters
Journal ArticleDOI
Glycine potentiates the NMDA response in cultured mouse brain neurons
J. W. Johnson,P Ascher +1 more
TL;DR: G glycine may facilitate excitatory transmission in the brain through an allosteric activation of the NMDA receptor, and can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists.
Journal ArticleDOI
Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum
David S. Bredt,Solomon H. Snyder +1 more
TL;DR: It is established that nitric oxide mediates the stimulation by glutamate of cGMP formation, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes.
Journal ArticleDOI
Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes
TL;DR: In voltage-clamped oocytes, neither perfusion nor rapid pressure application of NMDA onto messenger RNA-injected oocytes caused a distinct ionic current without added glycine, but when glycine was added, NMDA evoked large inward currents.
Journal ArticleDOI
Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists
Tage Honore,Steve N. Davies,Jorgen Drejer,E.J. Fletcher,Poul Jacobsen,David Lodge,Flemming Elmelund Nielsen +6 more
TL;DR: Quinoxalinediones have been found to be potent and competitive antagonists at non-NMDA glutamate receptors and will be useful in the determination of the structure-activity relations of quisqualate and kainate receptors and the role of such receptors in synaptic transmission in the mammalian brain.
Journal ArticleDOI
Direct signaling from astrocytes to neurons in cultures of mammalian brain cells
TL;DR: Astrocytes are shown to directly modulate the free cytosolic calcium, and hence transmission characteristics, of neighboring neurons, which suggests that the astrocytic-neuronal signaling is mediated through intercellular connections rather than synaptically.