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Regulation of Synaptic Strength by Protein Phosphatase 1
Open accessAbstract
We investigated the role of postsynaptic protein phosphatase 1 (PP1) in regulating synaptic strength by loading CA1 pyramidal cells either with peptides that disrupt PP1 binding to synaptic targeting proteins or with active PP1. The peptides blocked synaptically evoked LTD but had no effect on basal synaptic currents mediated by either AMPA or NMDA receptors. They did, however, cause an increase in synaptic strength following the induction of LTD. Similarly, PP1 had no effect on basal synaptic strength but enhanced LTD. In cultured neurons, synaptic activation of NMDA receptors increased the proportion of PP1 localized to synapses. These results suggest that PP1 does not significantly regulate basal synaptic strength. Appropriate NMDA receptor activation, however, allows PP1 to gain access to synaptic substrates and be recruited to synapses where its activity is necessary for sustaining LTD.
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“In a series of classic studies it was found that LTD is induced by the activation of a high-affinity Ca2+ cascade resulting in the activation of PP1 (395–397).”
From Synaptic memory and CaMKII (2023) · cites this paper as [396]
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“A previous study has reported that PP1 is recruited to synapses in response to NMDAR activation [50].”
From Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD (2009) · cites this paper as [50]
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Self-citation
Metadata
- Authors
- Morishita, W., Connor, J. H., Xia, H., Quinlan, E. M., Shenolikar, S., & Malenka, R. C.
- Affiliations
- Stanford Medicine (US)
- Duke Medical Center (US)
- University of Maryland, College Park (US)
- Corresponding author
- Malenka, Robert C
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 32
- Issue
- 6
- Pages
- 1133-1148
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1985405412
- Cited by
- 227
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 4 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH00942)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-52054, R01DK052054)
- 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
- protein phosphatase 1, synaptic efficacy, long-term depression, NMDA receptor activation, AMPA receptors, postsynaptic proteins, CA1 pyramidal neurons, synaptic plasticity
- MeSH terms
- Neurabins, Animals, Cells, Cultured, Hippocampus, Microfilament Proteins, Nerve Tissue Proteins, Neural Inhibition, Synaptic Transmission, Peptide Fragments, Phosphoprotein Phosphatases, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Long-Term Potentiation, Pyramidal Cells, Receptors, AMPA, Receptors, Metabotropic Glutamate, Excitatory Postsynaptic Potentials, Rats, Protein Phosphatase 1
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