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Science 304 (5673): 1021-1024

Copyright © 2004 by the American Association for the Advancement of Science

Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity

Lidong Liu,1* Tak Pan Wong,1* Mario F. Pozza,2 Kurt Lingenhoehl,2 Yushan Wang,1 Morgan Sheng,3 Yves P. Auberson,2 Yu Tian Wang1{dagger}

Abstract: Activation of N-methyl-D-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP. In contrast, preferential inhibition of NR2A-containing NMDARs prevents the induction of LTP without affecting LTD production. These results demonstrate that distinct NMDAR subunits are critical factors that determine the polarity of synaptic plasticity.

1 Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
2 Novartis Institutes of Biomedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland.
3 The Picower Center for Learning and Memory, RIKEN-Massachusetts Institute of Technology (MIT) Neuroscience Research Center, Howard Hughes Medical Institute (HHMI), MIT, 77 Massachusetts Avenue (E18-215), Cambridge, MA 02139, USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ytwang{at}interchange.ubc.ca

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M. Bjarnadottir, D. L. Misner, S. Haverfield-Gross, S. Bruun, V. G. Helgason, H. Stefansson, A. Sigmundsson, D. R. Firth, B. Nielsen, R. Stefansdottir, et al. (2007)
J. Neurosci. 27, 4519-4529
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Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus.
K. L. Meur, M. Galante, M. C. Angulo, and E. Audinat (2007)
J. Physiol. 580, 373-383
   Abstract »    Full Text »    PDF »
Modular Competition Driven by NMDA Receptor Subtypes in Spike-Timing-Dependent Plasticity.
R. C. Gerkin, P.-M. Lau, D. W. Nauen, Y. T. Wang, and G.-Q. Bi (2007)
J Neurophysiol 97, 2851-2862
   Abstract »    Full Text »    PDF »
NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo.
Y. Liu, T. P. Wong, M. Aarts, A. Rooyakkers, L. Liu, T. W. Lai, D. C. Wu, J. Lu, M. Tymianski, A. M. Craig, et al. (2007)
J. Neurosci. 27, 2846-2857
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Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis.
Q. Chen, S. He, X.-L. Hu, J. Yu, Y. Zhou, J. Zheng, S. Zhang, C. Zhang, W.-H. Duan, and Z.-Q. Xiong (2007)
J. Neurosci. 27, 542-552
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Synapse-specific regulation of AMPA receptor function by PSD-95.
J.-C. Beique, D.-T. Lin, M.-G. Kang, H. Aizawa, K. Takamiya, and R. L. Huganir (2006)
PNAS 103, 19535-19540
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Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex.
N. Origlia, N. Kuczewski, E. Aztiria, D. Gautam, J. Wess, and L. Domenici (2006)
J. Physiol. 577, 829-840
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Plasticity Compartments in Basal Dendrites of Neocortical Pyramidal Neurons.
U. Gordon, A. Polsky, and J. Schiller (2006)
J. Neurosci. 26, 12717-12726
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Insufficient Sleep Reversibly Alters Bidirectional Synaptic Plasticity and NMDA Receptor Function.
C. Kopp, F. Longordo, J. R. Nicholson, and A. Luthi (2006)
J. Neurosci. 26, 12456-12465
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Neural Cell Adhesion Molecule-associated Polysialic Acid Inhibits NR2B-containing N-Methyl-D-aspartate Receptors and Prevents Glutamate-induced Cell Death.
M. S. L. Hammond, C. Sims, K. Parameshwaran, V. Suppiramaniam, M. Schachner, and A. Dityatev (2006)
J. Biol. Chem. 281, 34859-34869
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Nursing-induced somatosensory cortex plasticity: temporally decoupled changes in neuronal receptive field properties are accompanied by modifications in activity-dependent protein expression..
C. Rosselet, Y. Zennou-Azogui, and C. Xerri (2006)
J. Neurosci. 26, 10667-10676
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Equilibrium Constants for (R)-[(S)-1-(4-Bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic Acid (NVP-AAM077) Acting at Recombinant NR1/NR2A and NR1/NR2B N-Methyl-D-aspartate Receptors: Implications for Studies of Synaptic Transmission.
P. A. Frizelle, P. E. Chen, and D. J. A. Wyllie (2006)
Mol. Pharmacol. 70, 1022-1032
   Abstract »    Full Text »    PDF »
Estradiol-Induced Increase in the Magnitude of Long-Term Potentiation Is Prevented by Blocking NR2B-Containing Receptors..
C. C. Smith and L. L. McMahon (2006)
J. Neurosci. 26, 8517-8522
   Abstract »    Full Text »    PDF »
Zinc modulates bidirectional hippocampal plasticity by effects on NMDA receptors..
Y. Izumi, Y. P. Auberson, and C. F. Zorumski (2006)
J. Neurosci. 26, 7181-7188
   Abstract »    Full Text »    PDF »

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