Cited by 310Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeurogenesis and neuroplasticity mechanisms

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PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory

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Volk, Lenora J., Bachman, Julia L., Johnson, Richard, Yu, Yilin, Huganir, Richard L.·2013·Nature

DOI 10.1038/nature11802PMC PMC3830948

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Abstract

Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.

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Authors: Volk, L. J., Bachman, J. L., Johnson, R., Yu, Y., & Huganir, R. L.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Huganir, Richard L.
ORCID: Volk, Lenora J.
Bachman, Julia L.
Johnson, Richard
Huganir, Richard L.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-01-02
Volume: 493
Issue: 7432
Pages: 420-423
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11802
PMC: PMC3830948
OpenAlex: W2063017515
Cited by: 310
References: 28
Citations by year: 2026: 7 · 2025: 6 · 2024: 15 · 2023: 7 · 2022: 10 · 2021: 17 · 2020: 10 · 2019: 24 · 2018: 22 · 2017: 33 · 2016: 33 · 2015: 37 · 2014: 37 · 2013: 50
FWCI: 25.67
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
National Institute of Mental Health (T32MH15330, T32MH015330)
National Eye Institute (T32EY017203)
National Institute of Neurological Disorders and Stroke (NS36715, P30NS050274, R01NS036715, R37NS036715)
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: PKM, protein kinase M, long-term potentiation, synaptic plasticity, learning and memory, protein kinase C, LTP maintenance, memory maintenance, hippocampus, memory formation, fear conditioning, spatial learning, conditioned taste aversion, place avoidance, PKCδ, protein kinase C epsilon
MeSH terms: Protein Kinase C zeta, Animals, Avoidance Learning, Behavior, Animal, Conditioning, Classical, Fear, Female, Hippocampus, Isoenzymes, Male, Synaptic Transmission, Neuronal Plasticity, Protein Kinase C, Synapses, Long-Term Potentiation, Mice, Knockout, Mice, Lipopeptides, Memory, Long-Term, Cell-Penetrating Peptides

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PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory

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