 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, November 26, 2003, 23(34):10791-10799
Previous Article | Next Article
Cellular/Molecular
Intracellular Domains of NMDA Receptor Subtypes Are Determinants for Long-Term Potentiation Induction
Georg Köhr,1 Vidar Jensen,3 Helmut J. Koester,2 Andre L. A. Mihaljevic,1 Jo K. Utvik,4 Ane Kvello,3 Ole P. Ottersen,4 Peter H. Seeburg,1 Rolf Sprengel,1 andØivind Hvalby3 1Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany, 2Baylor College of Medicine, Houston, Texas 77030, and 3Institute of Basic Medical Sciences and 4Centre for Molecular Biology and Neuroscience and Department of Anatomy, University of Oslo, N-0317 Oslo, Norway
NMDA receptors (NMDARs) are essential for modulating synaptic strength at central synapses. At hippocampal CA3-to-CA1 synapses of adult mice, different NMDAR subtypes with distinct functionality assemble from NR1 with NR2A and/or NR2B subunits. Here we investigated the role of these NMDA receptor subtypes in long-term potentiation (LTP) induction. Because of the higher NR2B contribution in the young hippocampus, LTP of extracellular field potentials could be enhanced by repeated tetanic stimulation in young but not in adult mice. Similarly, NR2B-specific antagonists reduced LTP in young but only marginally in adult wild-type mice, further demonstrating that in mature CA3-to-CA1 connections LTP induction results primarily from NR2A-type signaling. This finding is also supported by gene-targeted mutant mice expressing C-terminally truncated NR2A subunits, which participate in synaptic NMDAR channel formation and Ca2+ signaling, as indicated by immunopurified synaptic receptors, postembedding immunogold labeling, and spinous Ca2+ transients in the presence of NR2B blockers. These blockers abolished LTP in the mutant at all ages, revealing that, without the intracellular C-terminal domain, NR2A-type receptors are deficient in LTP signaling. Without NR2B blockade, CA3-to-CA1 LTP was more strongly reduced in adult than young mutant mice but could be restored to wild-type levels by repeated tetanic stimulation. Thus, besides NMDA receptor-mediated Ca2+ influx, subtype-specific signaling is critical for LTP induction, with the intracellular C-terminal domain of the NR2 subunits directing signaling pathways with an age-dependent preference.
Key words: gene-targeted mouse; hippocampal CA3-to-CA1 LTP; postembedding immunogold labeling; coimmunoprecipitation; NR2B antagonists; two-photon imaging; spinous calcium transients; signal transduction
Received Aug 20, 2003; revised September 12, 2003; accepted September 22, 2003.
This article has been cited by other articles:
R. Kimura and N. Matsuki
Protein kinase CK2 modulates synaptic plasticity by modification of synaptic NMDA receptors in the hippocampus
J. Physiol., July 1, 2008; 586(13): 3195 - 3206.
[Abstract] [Full Text] [PDF]
D. M. Bannerman, B. Niewoehner, L. Lyon, C. Romberg, W. B. Schmitt, A. Taylor, D. J. Sanderson, J. Cottam, R. Sprengel, P. H. Seeburg, et al.
NMDA Receptor Subunit NR2A Is Required for Rapidly Acquired Spatial Working Memory But Not Incremental Spatial Reference Memory
J. Neurosci., April 2, 2008; 28(14): 3623 - 3630.
[Abstract] [Full Text] [PDF]
A. Z. Harris and D. L. Pettit
Recruiting Extrasynaptic NMDA Receptors Augments Synaptic Signaling
J Neurophysiol, February 1, 2008; 99(2): 524 - 533.
[Abstract] [Full Text] [PDF]
R. C. Ewald, K. R. Van Keuren-Jensen, C. D. Aizenman, and H. T. Cline
Roles of NR2A and NR2B in the Development of Dendritic Arbor Morphology In Vivo
J. Neurosci., January 23, 2008; 28(4): 850 - 861.
[Abstract] [Full Text] [PDF]
J.-P. Zhao and M. Constantine-Paton
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. Neurosci., December 12, 2007; 27(50): 13649 - 13654.
[Abstract] [Full Text] [PDF]
Y. Zhou, E. Takahashi, W. Li, A. Halt, B. Wiltgen, D. Ehninger, G.-D. Li, J. W. Hell, M. B. Kennedy, and A. J. Silva
Interactions between the NR2B Receptor and CaMKII Modulate Synaptic Plasticity and Spatial Learning
J. Neurosci., December 12, 2007; 27(50): 13843 - 13853.
[Abstract] [Full Text] [PDF]
A. Z. Harris and D. L. Pettit
Extrasynaptic and synaptic NMDA receptors form stable and uniform pools in rat hippocampal slices
J. Physiol., October 15, 2007; 584(2): 509 - 519.
[Abstract] [Full Text] [PDF]
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
Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor
J. Neurosci., September 19, 2007; 27(38): 10185 - 10195.
[Abstract] [Full Text] [PDF]
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.
NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo
J. Neurosci., March 14, 2007; 27(11): 2846 - 2857.
[Abstract] [Full Text] [PDF]
M. S. L. Hammond, C. Sims, K. Parameshwaran, V. Suppiramaniam, M. Schachner, and A. Dityatev
Neural Cell Adhesion Molecule-associated Polysialic Acid Inhibits NR2B-containing N-Methyl-D-aspartate Receptors and Prevents Glutamate-induced Cell Death
J. Biol. Chem., November 17, 2006; 281(46): 34859 - 34869.
[Abstract] [Full Text] [PDF]
E. A. Waxman and D. R. Lynch
N-Methyl-D-aspartate Receptor Subtype Mediated Bidirectional Control of p38 Mitogen-activated Protein Kinase
J. Biol. Chem., August 12, 2005; 280(32): 29322 - 29333.
[Abstract] [Full Text] [PDF]
S. Berberich, P. Punnakkal, V. Jensen, V. Pawlak, P. H. Seeburg, O. Hvalby, and G. Kohr
Lack of NMDA Receptor Subtype Selectivity for Hippocampal Long-Term Potentiation
J. Neurosci., July 20, 2005; 25(29): 6907 - 6910.
[Abstract] [Full Text] [PDF]
S. Qiu, Y.-l. Hua, F. Yang, Y.-z. Chen, and J.-h. Luo
Subunit Assembly of N-Methyl-D-aspartate Receptors Analyzed by Fluorescence Resonance Energy Transfer
J. Biol. Chem., July 1, 2005; 280(26): 24923 - 24930.
[Abstract] [Full Text] [PDF]
C.-H. Yang, C.-C. Huang, and K.-S. Hsu
Behavioral Stress Enhances Hippocampal CA1 Long-Term Depression through the Blockade of the Glutamate Uptake
J. Neurosci., April 27, 2005; 25(17): 4288 - 4293.
[Abstract] [Full Text] [PDF]
Y. N. Dong, E. A. Waxman, and D. R. Lynch
Interactions of Postsynaptic Density-95 and the NMDA Receptor 2 Subunit Control Calpain-Mediated Cleavage of the NMDA Receptor
J. Neurosci., December 8, 2004; 24(49): 11035 - 11045.
[Abstract] [Full Text] [PDF]
S. B. Mierau, R. M. Meredith, A. L. Upton, and O. Paulsen
Dissociation of experience-dependent and -independent changes in excitatory synaptic transmission during development of barrel cortex
PNAS, October 26, 2004; 101(43): 15518 - 15523.
[Abstract] [Full Text] [PDF]
S. G. Cull-Candy and D. N. Leszkiewicz
Role of Distinct NMDA Receptor Subtypes at Central Synapses
Sci. Signal., October 19, 2004; 2004(255): re16 - re16.
[Abstract] [Full Text] [PDF]
T. P. Wong, L. Liu, M. Sheng, and Y. T. Wang
Response to Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity"
Science, September 24, 2004; 305(5692): 1912c - 1912c.
[Full Text] [PDF]
D. B. Scott, I. Michailidis, Y. Mu, D. Logothetis, and M. D. Ehlers
Endocytosis and Degradative Sorting of NMDA Receptors by Conserved Membrane-Proximal Signals
J. Neurosci., August 11, 2004; 24(32): 7096 - 7109.
[Abstract] [Full Text] [PDF]
L. Liu, T. P. Wong, M. F. Pozza, K. Lingenhoehl, Y. Wang, M. Sheng, Y. P. Auberson, and Y. T. Wang
Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity
Science, May 14, 2004; 304(5673): 1021 - 1024.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|