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Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery


Anatomical and electrophysiological experiments1,2,3,4,5,6 show that central excitatory synapses initially display NMDA (N-methyl-d-aspartate) receptors (NMDARs) and subsequently mature by acquiring AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs). NMDAR activation can lead to rapid synaptic delivery of AMPARs ('AMPAfication')7,8, but the view that AMPAfication during development requires NMDAR activation has been challenged by studies showing that chronic removal of NMDAR function (either genetically9,10 or pharmacologically11,12,13,14) has no apparent effect on acquisition of AMPAR-mediated synaptic transmission. Here we show that NMDARs are crucial in the developmental acquisition of AMPAR-mediated synaptic transmission, and that chronic disabling of NMDAR function triggers compensatory mechanisms for NMDAR-independent AMPAfication.

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Figure 1: Effects of acute and chronic blockade of NMDA receptors on glutamatergic synapses in hippocampus.

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We thank N. Dawkins-Pisani for technical assistance, and H. Cline and members of the Malinow laboratory for helpful comments and discussions. This study was supported by the National Institutes of Health (R.M.), the Alle Davis and Maxine Harrison Endowment (R.M.), the Alzheimer's Association (J.J.Z.) and the Fraxa Medical Research Foundation (J.J.Z.). J.J.Z. is a Naples Investigator of the NARSAD (National Alliance for Research on Schizophrenia and Depression) Foundation.

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Correspondence to Roberto Malinow.

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Zhu, J., Malinow, R. Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery. Nat Neurosci 5, 513–514 (2002).

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