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Astroglial contribution to NMDA receptor activity

Understanding the properties of NMDARs and their regulation by the local environment is of paramount importance for the sake of our central nervous system. The possibility that the glycine-site of NMDARs could represent an important pathway to regulate NMDAR activity was disregarded for a long time because based on the belief that this site was fully saturated by ambient glycine. We now know that glycine is not the only endogenous co-agonist of NMDARs and that both glycine and D-serine can differentially regulate the activity of these glutamatergic receptors. We will here review our latest results describing the key roles played by astroglial Ca2+, IP3 and membrane receptors in providing D-serine at excitatory synapses and how these processes impact synaptic plasticity and behavior in both a physiological and pathological context.