Glia-derived D-serine controls NMDA receptor activity and synaptic memory.
The NMDA receptor is a key player in excitatory transmission and synaptic plasticity in the central nervous system. Its activation requires the binding of both glutamate and a co-agonist like D-serine to its glycine site. As D-serine is released exclusively by astrocytes, we studied the physiological impact of the glial environment on NMDA receptor-dependent activity and plasticity. To this end, we took advantage of the changing astrocytic ensheathing of neurons occurring in the supraoptic nucleus during lactation. We provide direct evidence that in this hypothalamic structure the endogenous co-agonist of NMDA receptors is D-serine and not glycine. Consequently, the degree of astrocytic coverage of neurons governs the level of glycine site occupancy on the NMDA receptor, thereby affecting their availability for activation and thus the activity dependence of long-term synaptic changes. Such a contribution of astrocytes to synaptic metaplasticity fuels the emerging concept that astrocytes are dynamic partners of brain signaling.
Panatier
Aude
A
Inserm, U378, Bordeaux, F-33077, France.
Theodosis
Dionysia T
DT
Mothet
Jean-Pierre
JP
Touquet
Bastien
B
Pollegioni
Loredano
L
Poulain
Dominique A
DA
Oliet
Stéphane H R
SH
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005260:Female; D007774:Lactation / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019998:Racemases and Epimerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D000099300:Serine Racemase
D018691:Excitatory Amino Acid Antagonists; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase