Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein.
Abstract
Specific patterns of neuronal firing induce changes in synaptic strength that may contribute to learning and memory. If the postsynaptic NMDA (N-methyl-D-aspartate) receptors are blocked, long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and the learning of spatial information are prevented. The NMDA receptor can bind a protein known as postsynaptic density-95 (PSD-95), which may regulate the localization of and/or signalling by the receptor. In mutant mice lacking PSD-95, the frequency function of NMDA-dependent LTP and LTD is shifted to produce strikingly enhanced LTP at different frequencies of synaptic stimulation. In keeping with neural-network models that incorporate bidirectional learning rules, this frequency shift is accompanied by severely impaired spatial learning. Synaptic NMDA-receptor currents, subunit expression, localization and synaptic morphology are all unaffected in the mutant mice. PSD-95 thus appears to be important in coupling the NMDA receptor to pathways that control bidirectional synaptic plasticity and learning.
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Mice null for PSD-95 and those carrying truncated PSD-95 show markedly enhanced LTP.
“Indeed, mice null for PSD-95 and those carrying truncated PSD-95 show markedly enhanced LTP [23],[24].”
From Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD (2009) · cites this paper as [23]
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- Authors
- Migaud, M., Charlesworth, P., Dempster, M., Webster, L. C., Watabe, A. M., Makhinson, M., He, Y., Ramsay, M. F., Morris, R. G. M., Morrison, J. H., O'Dell, T. J., & Grant, S. G. N.
- Affiliations
- University of Edinburgh (GB)
- University of California, Los Angeles (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Grant, Seth G. N.
- ORCID
- Venue
- Nature
- Published
- 1998-12
- Volume
- 396
- Issue
- 6710
- Pages
- 433-439
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1624178692
- Cited by
- 1,160
- References
- 2
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 26 · 2023: 25 · 2022: 28 · 2021: 37 · 2020: 32 · 2019: 39 · 2018: 47 · 2017: 47 · 2016: 36 · 2015: 34 · 2014: 47 · 2013: 39 · 2012: 26
- FWCI
- 17.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- PSD-95, long-term potentiation, long-term depression, NMDA receptor, synaptic plasticity, spatial learning, learning and memory
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Electrophysiology, Hippocampus, Learning, Learning Disabilities, Membrane Proteins, Memory, Mice, Inbred C57BL, Models, Neurological, Mutation, Nerve Tissue Proteins, Synapses, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Gene Targeting, Maze Learning, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases
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