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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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Amygdala infusions of an NR2B-selective or an NR2A-preferring NMDA receptor antagonist differentially influence fear conditioning and expression in the fear-potentiated startle test.
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Learn. Mem. 15, 67-74
   Abstract »    Full Text »    PDF »
Roles of NR2A and NR2B in the Development of Dendritic Arbor Morphology In Vivo.
R. C. Ewald, K. R. Van Keuren-Jensen, C. D. Aizenman, and H. T. Cline (2008)
J. Neurosci. 28, 850-861
   Abstract »    Full Text »    PDF »
Thrombin Induces Long-Term Potentiation of Reactivity to Afferent Stimulation and Facilitates Epileptic Seizures in Rat Hippocampal Slices: Toward Understanding the Functional Consequences of Cerebrovascular Insults.
N. Maggio, E. Shavit, J. Chapman, and M. Segal (2008)
J. Neurosci. 28, 732-736
   Abstract »    Full Text »    PDF »
Mechanisms Underlying Dedepression of Synaptic NMDA Receptors in the Hippocampus.
W. Morishita and R. C. Malenka (2008)
J Neurophysiol 99, 254-263
   Abstract »    Full Text »    PDF »
Mitochondrial Sensitivity and Altered Calcium Handling Underlie Enhanced NMDA-Induced Apoptosis in YAC128 Model of Huntington's Disease.
H. B. Fernandes, K. G. Baimbridge, J. Church, M. R. Hayden, and L. A. Raymond (2007)
J. Neurosci. 27, 13614-13623
   Abstract »    Full Text »    PDF »
NR2A / Mice Lack Long-Term Potentiation But Retain NMDA Receptor and L-Type Ca2+ Channel-Dependent Long-Term Depression in the Juvenile Superior Colliculus.
J.-P. Zhao and M. Constantine-Paton (2007)
J. Neurosci. 27, 13649-13654
   Abstract »    Full Text »    PDF »
On the Hypes and Falls in Neuroprotection: Targeting the NMDA Receptor.
C. Villmann and C.-M. Becker (2007)
Neuroscientist 13, 594-615
   Abstract »    PDF »
Synaptic Plasticity (and the Lack Thereof) in Hippocampal CA2 Neurons.
M. Zhao, Y.-S. Choi, K. Obrietan, and S. M. Dudek (2007)
J. Neurosci. 27, 12025-12032
   Abstract »    Full Text »    PDF »
Tyrosine Phosphorylation Sites in ephrinB2 Are Required for Hippocampal Long-Term Potentiation But Not Long-Term Depression.
F. Bouzioukh, G. A. Wilkinson, G. Adelmann, M. Frotscher, V. Stein, and R. Klein (2007)
J. Neurosci. 27, 11279-11288
   Abstract »    Full Text »    PDF »
Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices.
A. Z. Harris and D. L. Pettit (2007)
J. Physiol. 584, 509-519
   Abstract »    Full Text »    PDF »
Nicotine Regulates Multiple Synaptic Proteins by Inhibiting Proteasomal Activity.
K. Rezvani, Y. Teng, D. Shim, and M. De Biasi (2007)
J. Neurosci. 27, 10508-10519
   Abstract »    Full Text »    PDF »
Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor.
A. Fontan-Lozano, J. L. Saez-Cassanelli, M. C. Inda, M. de los Santos-Arteaga, S. A. Sierra-Dominguez, G. Lopez-Lluch, J. M. Delgado-Garcia, and A. M. Carrion (2007)
J. Neurosci. 27, 10185-10195
   Abstract »    Full Text »    PDF »
Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairment.
T. P. Wong, J. G. Howland, J. M. Robillard, Y. Ge, W. Yu, A. K. Titterness, K. Brebner, L. Liu, J. Weinberg, B. R. Christie, et al. (2007)
PNAS 104, 11471-11476
   Abstract »    Full Text »    PDF »
N-Methyl-D-aspartate Receptor-dependent Regulation of the Glutamate Transporter Excitatory Amino Acid Carrier 1.
E. A. Waxman, I. Baconguis, D. R. Lynch, and M. B. Robinson (2007)
J. Biol. Chem. 282, 17594-17607
   Abstract »    Full Text »    PDF »

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