Glia-derived D-serine controls NMDA receptor activity and synaptic memory.
Cell. 2006-05-01; 125(4): 775-784
DOI: 10.1016/j.cell.2006.02.051
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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.