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  Intracellular domains of the NMDA receptor subtypes are determinants for long-term potentiation induction

Köhr, G., Jensen, V., Köster, H. J., Mihaljevic, A., Utvik, J. K., Kvello, A., et al. (2003). Intracellular domains of the NMDA receptor subtypes are determinants for long-term potentiation induction. The Journal of Neuroscience, 23(34), 10791-10799. Retrieved from http://www.jneurosci.org/content/23/34/10791.abstract.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-BA3C-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-BA3D-D
Genre: Journal Article
Alternative Title : Intracellular domains of the NMDA receptor subtypes are determinants for long-term potentiation induction

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 Creators:
Köhr, Georg1, Author              
Jensen, Vidar, Author
Köster, Helmut Joachim2, Author              
Mihaljevic, André1, Author              
Utvik, Jo Kristian, Author
Kvello, Ane, Author
Ottersen, Ole Petter, Author
Seeburg, Peter H.1, Author              
Sprengel, Rolf1, Author              
Hvalby, Øivind, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: gene-targeted mouse; hippocampal CA3-to-CA1 LTP; postembedding immunogold labeling; coimmunoprecipitation; NR2B antagonists; two-photon imaging; spinous calcium transients; signal transduction
 Abstract: 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.

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Language(s): eng - English
 Dates: 2003-09-122003-08-202003-09-222003-11-26
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

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Title: The Journal of Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 23 (34) Sequence Number: - Start / End Page: 10791 - 10799 Identifier: ISSN: 0270-6474
CoNE: /journals/resource/954925502187