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Science 14 May 2004:
Vol. 304. no. 5673, pp. 1021 - 1024
DOI: 10.1126/science.1096615
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Reports

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}

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.



* 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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Behavioral Stress Enhances Hippocampal CA1 Long-Term Depression through the Blockade of the Glutamate Uptake.
C.-H. Yang, C.-C. Huang, and K.-S. Hsu (2005)
J. Neurosci. 25, 4288-4293
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Diminished Neuronal Activity Increases Neuron-Neuron Connectivity Underlying Silent Synapse Formation and the Rapid Conversion of Silent to Functional Synapses.
K. Nakayama, K. Kiyosue, and T. Taguchi (2005)
J. Neurosci. 25, 4040-4051
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Reduced glycine transporter type 1 expression leads to major changes in glutamatergic neurotransmission of CA1 hippocampal neurones in mice.
M. Martina, M.-E. B.-Turcotte, S. Halman, G. Tsai, M. Tiberi, J. T Coyle, and R. Bergeron (2005)
J. Physiol. 563, 777-793
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Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles.
K. Erreger, S. M Dravid, T. G Banke, D. J. A Wyllie, and S. F Traynelis (2005)
J. Physiol. 563, 345-358
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Regulation of the NMDA Receptor Complex and Trafficking by Activity-Dependent Phosphorylation of the NR2B Subunit PDZ Ligand.
H. J. Chung, Y. H. Huang, L.-F. Lau, and R. L. Huganir (2004)
J. Neurosci. 24, 10248-10259
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Role of Distinct NMDA Receptor Subtypes at Central Synapses.
S. G. Cull-Candy and D. N. Leszkiewicz (2004)
Sci. STKE 2004, re16
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Switching of NMDA Receptor 2A and 2B Subunits at Thalamic and Cortical Synapses during Early Postnatal Development.
X.-B. Liu, K. D. Murray, and E. G. Jones (2004)
J. Neurosci. 24, 8885-8895
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Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity".
D. A. Rusakov, A. Scimemi, M. C. Walker, and D. M. Kullmann (2004)
Science 305, 1912b
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Response to Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity".
T. P. Wong, L. Liu, M. Sheng, and Y. T. Wang (2004)
Science 305, 1912c
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Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression.
P. V. Massey, B. E. Johnson, P. R. Moult, Y. P. Auberson, M. W. Brown, E. Molnar, G. L. Collingridge, and Z. I. Bashir (2004)
J. Neurosci. 24, 7821-7828
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Chronic Ethanol Induces Synaptic But Not Extrasynaptic Targeting of NMDA Receptors.
E. P. Carpenter-Hyland, J. J. Woodward, and L. J. Chandler (2004)
J. Neurosci. 24, 7859-7868
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