Mobility of NMDA autoreceptors but not postsynaptic receptors at glutamate synapses in the rat entorhinal cortex


NMDA receptors (NMDAr) are known to undergo recycling and lateral diffusion in postsynaptic spines and dendrites. However, NMDAr are also present as autoreceptors on glutamate terminals, where they act to facilitate glutamate release, but it is not known whether these receptors are also mobile. We have used functional pharmacological approaches to examine whether NMDA receptors at excitatory synapses in the rat entorhinal cortex are mobile at either postsynaptic sites or in presynaptic terminals. When NMDAr-mediated evoked EPSCs (eEPSCs) were blocked by MK-801, they showed no evidence of recovery when the irreversible blocker was removed, suggesting that postsynaptic NMDAr were relatively stably anchored at these synapses. However, using frequency-dependent facilitation of AMPA receptor (AMPAr)-mediated eEPSCs as a reporter of presynaptic NMDAr activity, we found that when facilitation was blocked with MK-801 there was a rapid (similar to 30-40 min) anomalous recovery upon removal of the antagonist. This was not observed when global NMDAr blockade was induced by combined perfusion with MK-801 and NMDA. Anomalous recovery was accompanied by an increase in frequency of spontaneous EPSCs, and a variable increase in frequency-facilitation. Following recovery from blockade of presynaptic NMDAr with a competitive antagonist, frequency-dependent facilitation of AMPAr-mediated eEPSCs was also transiently enhanced. Finally, an increase in frequency of miniature EPSCs induced by NMDA was succeeded by a persistent decrease. Our data provide the first evidence for mobility of NMDAr in the presynaptic terminals, and may point to a role of this process in activity-dependent control of glutamate release.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
College of Health & Life Sciences
Uncontrolled Keywords: Physiology
Publication ISSN: 1469-7793
Last Modified: 02 Jan 2024 08:32
Date Deposited: 23 Sep 2013 11:09
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2008-10-15
Published Online Date: 2008-08-21
Authors: Yang, Jian
Chamberlain, Sophie E.L.
Woodhall, Gavin L. (ORCID Profile 0000-0003-1281-9008)
Jones, Roland S.G.



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