Contribution of Hippocampal and Extra-Hippocampal NR2B-Containing NMDA Receptors to Performance on Spatial Learning Tasks
Open accessAbstract
Controversy revolves around the differential contribution of NR2A- and NR2B-containing NMDA receptors, which coexist in principal forebrain neurons, to synaptic plasticity and learning in the adult brain. Here, we report genetically modified mice in which the NR2B subunit is selectively ablated in principal neurons of the entire postnatal forebrain or only the hippocampus. NR2B ablation resulted in smaller NMDA receptor-mediated EPSCs with accelerated decay kinetics, as recorded in CA1 pyramidal cells. CA3-to-CA1 field LTP remained largely unaltered, although a pairing protocol revealed decreased NMDA receptor-mediated charge transfer and reduced cellular LTP. Mice lacking NR2B in the forebrain were impaired on a range of memory tasks, presenting both spatial and nonspatial phenotypes. In contrast, hippocampus-specific NR2B ablation spared hippocampus-dependent, hidden-platform water maze performance but induced a selective, short-term, spatial working memory deficit for recently visited places. Thus, both hippocampal and extra-hippocampal NR2B containing NMDA receptors critically contribute to spatial performance.
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Removal of the GluN2B subunit by knockout or knockdown produces variable effects on LTP, ranging from complete block to partial impairment.
“The first approach removed the GluN2B subunit, either by knockout or knockdown. The results vary from a complete block of LTP (226, 227) to a partial impairment (228, 229).”
From Synaptic memory and CaMKII (2023) · cites this paper as [228]
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- Authors
- von Engelhardt, J., Doganci, B., Jensen, V., Hvalby, Ø., Göngrich, C., Taylor, A., Barkus, C., Sanderson, D. J., Rawlins, J. N. P., Seeburg, P. H., Bannerman, D. M., & Monyer, H.
- Affiliations
- Heidelberg University (DE)
- University of Oslo (NO)
- University of Oxford (GB)
- Max Planck Institute for Medical Research (DE)
- Corresponding author
- Monyer, Hannah
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 60
- Issue
- 5
- Pages
- 846-860
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2018213389
- Cited by
- 250
- References
- 5
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 10 · 2020: 6 · 2019: 18 · 2018: 12 · 2017: 11 · 2016: 22 · 2015: 14 · 2014: 16 · 2013: 21 · 2012: 30
- FWCI
- 6.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1720 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Durham Research Online (Durham University) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (SRF 074385/Z/04/Z, 087736)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- NR2A subunit, hippocampus, spatial learning, spatial working memory, long-term potentiation, CA1 pyramidal neurons, excitatory postsynaptic potentials, synaptic plasticity, memory impairment, genetically modified mice
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Electron Transport Complex IV, Discrimination, Psychological, Electric Stimulation, Evoked Potentials, Exploratory Behavior, Female, Hippocampus, Male, Membrane Potentials, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neurons, Photic Stimulation, Space Perception, Receptors, N-Methyl-D-Aspartate, Patch-Clamp Techniques, Excitatory Amino Acid Agents, Maze Learning, Excitatory Postsynaptic Potentials, Recognition, Psychology, Mice, In Vitro Techniques
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