IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(1):47-56.

Original Article
Reciprocal and activity-dependent regulation of surface AMPA and NMDA receptors
in cultured neurons

Guo Hua Li, Michael F. Jackson, Beverley A. Orser, John F. MacDonald

Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Robarts
Research Institute, Department of Physiology and Pharmacology, Department of Anatomy and Cell biology, University of Western
Ontario, London, Ontario; Departments of Anesthesia, Department of Physiology, University of Toronto, Toronto, Ontario, Canada

Received December 7, 2009; accepted December 20, 2009; available online January 1, 2010

Abstract: Activation of NMDA receptors (NMDARs) can modulate excitatory synaptic transmission in the central nervous system by
dynamically altering the number of synaptic AMPA receptors (AMPARs).  The surface expression of NMDARs themselves is also subject
to modulation in an activity-dependent manner.  In addition to NMDAR-induced changes in AMPAR expression, AMPARs have also been
found to regulate their own surface expression, independently of NMDARs.  However, whether or not AMPARs and NMDARs might
reciprocally regulate their surface expression has not previously been systematically explored.  We utilized surface biotinylation assays
and stimulation protocols intended to selectively stimulate various glutamate receptor subpopulations (e.g. AMPARs vs NMDARs;
synaptic vs extrasynaptic).  We reveal that activation of synaptic NMDA receptors increases the surface expression of both NMDAR and
AMPAR subunits, while activation of extrasynaptic NMDAR produces the opposite effect.  Surprisingly, we find that selective activation of
AMPARs reduces the surface expression of not only AMPARs but also of NMDARs.  These results suggest that both AMPARs and
NMDARs at synaptic sites are subject to modulation by multiple signalling pathways in an activity-dependent way.(IJPPP912001).

Key words: AMPA receptor, NMDA receptor, trafficking; synaptic, extrasynaptic, surface expression

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Address all correspondence to:
Dr. Michael F. Jackson
Robarts Research Institute
University of Western Ontario
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London, Ontario N6A 5K8
E-mail:
mjackson@robarts.ca