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Cited by 172Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

Opposing effects of PSD‐93 and PSD‐95 on long‐term potentiation and spike timing‐dependent plasticity

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Carlisle, Holly J., Fink, Ann E., Grant, Seth G. N., O’Dell, Thomas J.·2008·The Journal of Physiology
DOI 10.1113/jphysiol.2008.163469PMC PMC2655416
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Abstract

The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity. While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether these MAGUKs also have functionally similar roles in synaptic plasticity. To explore this issue we examined several properties of basal synaptic transmission in the hippocampal CA1 region of PSD-93 and PSD-95 mutant mice and compared the ability of a number of different synaptic stimulation protocols to induce long-term potentiation (LTP) and long-term depression (LTD) in these mutants. We find that while both AMPA and NMDA receptor-mediated synaptic transmission are normal in PSD-93 mutants, PSD-95 mutant mice exhibit clear deficits in AMPA receptor-mediated transmission. Moreover, in contrast to the facilitation of LTP induction and disruption of LTD observed in PSD-95 mutant mice, PSD-93 mutant mice exhibit deficits in LTP and normal LTD. Our results suggest that PSD-95 has a unique role in AMPA receptor trafficking at excitatory synapses in the hippocampus of adult mice and indicate that PSD-93 and PSD-95 have essentially opposite roles in LTP, perhaps because these MAGUKs form distinct NMDA receptor signalling complexes that differentially regulate the induction of LTP by different patterns of synaptic activity.

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  • Knocking out PSD-95 does not prevent LTP.

    “Furthermore, knocking out PSD-95 does not prevent LTP (299).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [299]

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Cited by

Sorted by citations

Authors
Carlisle, H. J., Fink, A. E., Grant, S. G. N., & O’Dell, T. J.
Affiliations
  • University of California, Los Angeles (US)
  • Wellcome Sanger Institute (GB)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2008-12-12
Volume
586
Issue
24
Pages
5885-5900
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2008.163469
PMC
PMC2655416
OpenAlex
W2133193505
Cited by
172
References
6
Citations by year
2026: 6 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 10 · 2021: 17 · 2020: 11 · 2019: 7 · 2018: 19 · 2017: 15 · 2016: 10 · 2015: 8 · 2014: 10 · 2013: 10 · 2012: 12
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Wellcome Trust
  • National Institutes of Health
  • National Institute of Mental Health (MH609197)
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-93, PSD-95, SAP102, membrane-associated guanylate kinase, long-term potentiation, long-term depression, spike-timing-dependent plasticity, AMPA receptor trafficking, synaptic plasticity, hippocampal CA1, mouse mutants
MeSH terms
Disks Large Homolog 4 Protein, Action Potentials, Animals, Electric Stimulation, Hippocampus, Lidocaine, Male, Membrane Proteins, Mice, Inbred C57BL, Synaptic Transmission, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Pyramidal Cells, Receptors, AMPA, Mice, Knockout, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, Sodium Channel Blockers, Long-Term Synaptic Depression, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases

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