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Glia-Derived d-Serine Controls NMDA Receptor Activity and Synaptic Memory

Glia-Derived d-Serine Controls NMDA Receptor Activity and Synaptic Memory,10.1016/j.cell.2006.02.051,Cell,Aude Panatier,Dionysia T. Theodosis,Jean-Pie

Glia-Derived d-Serine Controls NMDA Receptor Activity and Synaptic Memory   (Citations: 140)
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SUMMARY The NMDA receptor is a key player in excitatory transmission and synaptic plasticity in the cen- tral nervous system. Its activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. As D-serine is re- leased exclusively by astrocytes, we studied the physiological impact of the glial environ- ment on NMDA receptor-dependent activity and plasticity. To this end, we took advantage of the changing astrocytic ensheathing of neu- rons occurring in the supraoptic nucleus during lactation. We provide direct evidence that in this hypothalamic structure the endogenous coagonist of NMDA receptors is D-serine and not glycine. Consequently, the degree of astro- cytic 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 astro- cytes to synaptic metaplasticity fuels the emerg- ingconceptthatastrocytesaredynamicpartners of brain signaling.
Journal: Cell , vol. 125, no. 4, pp. 775-784, 2006
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