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Postsynaptic Density-95 Mimics and Occludes Hippocampal Long-Term Potentiation and Enhances Long-Term Depression
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Previous studies have shown that overexpression of the protein PSD-95 (postsynaptic density-95) selectively enhances AMPA receptor-mediated synaptic responses in hippocampal pyramidal cells. To determine whether this effect is related to synaptic plasticity at these synapses, we examined whether PSD-95 expression mimics long-term potentiation (LTP), and also whether it influences LTP and long-term depression (LTD) in hippocampal slice cultures. Using simultaneous recording from transfected or infected cells and control pyramidal cells, we found that PSD-95, similar to LTP, increases the amplitude and frequency of miniature EPSCs. It also converts silent synapses to functional synapses, as does LTP. In addition, LTP is completely occluded in cells expressing PSD-95, whereas LTD is greatly enhanced. These results suggest that common mechanisms are involved in controlling synaptic AMPA receptors by PSD-95 and synaptic plasticity.
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“since overexpression of PSD-95 on its own potentiates AMPAR EPSCs and occludes LTP (131, 297, 298) and the S73D mutant causes a similar potentiation.”
From Synaptic memory and CaMKII (2023) · cites this paper as [297]
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“The quantity of surface receptors controls synaptic strength [57-59]; therefore, reduction of both synaptic transmission and plasticity in the Shank3 heterozygotes would support a mechanism involving altered AMPA receptor trafficking.”
From Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication (2010) · cites this paper as [59]
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Metadata
- Authors
- Stein, V., House, D. R. C., Bredt, D. S., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-07-02
- Volume
- 23
- Issue
- 13
- Pages
- 5503-5506
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741246
- OpenAlex
- W2155715182
- Cited by
- 341
- References
- 15
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 13 · 2022: 10 · 2021: 10 · 2020: 18 · 2019: 16 · 2018: 11 · 2017: 15 · 2016: 15 · 2015: 14 · 2014: 15 · 2013: 18 · 2012: 11
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Bristol-Myers Squibb
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Center for Neuroscience Research
- National Cancer Institute (R01CA094143)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- PSD-95, postsynaptic density, long-term potentiation, long-term depression, synaptic plasticity, AMPA receptors, hippocampal pyramidal neurons, miniature EPSCs, silent synapses, synaptic transmission, hippocampal slice cultures
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Cells, Cultured, Hippocampus, Humans, Luminescent Proteins, Membrane Proteins, Nerve Tissue Proteins, Neuronal Plasticity, Recombinant Fusion Proteins, Synapses, Transfection, Long-Term Potentiation, Pyramidal Cells, Receptors, AMPA, Excitatory Postsynaptic Potentials, Long-Term Synaptic Depression, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins, Rats, In Vitro Techniques
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