ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
ZIP It: Neural Silencing Is an Additional Effect of the PKM-Zeta Inhibitor Zeta-Inhibitory Peptide.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- A neural circuit for sex-dependent conditioned pain hypersensitivity in mice.Nature communications · 2025Article
- PKMζ drives spatial memory reconsolidation but not maintenance.Frontiers in synaptic neuroscience · 2025Article
- Cationic peptides erase memories by removing synaptic AMPA receptors through endophilin-mediated endocytosis.Research square · 2023Article
- Photoactivated Protein Degrader for Optical Control of Synaptic Function.ACS chemical neuroscience · 2023Article
- A Photoactivated Protein Degrader for Optical Control of Synaptic Function.bioRxiv : the preprint server for biology · 2023Article
- The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Infusing zeta inhibitory peptide into the perirhinal cortex of rats abolishes long-term object recognition memory without affecting novel object location recognition.Frontiers in behavioral neuroscience · 2022Article
- Involvement of PKMζ in Stress Response and Depression.Frontiers in cellular neuroscience · 2022Review
- A critical role for long-term potentiation mechanisms in the maintenance of object recognition memory in perirhinal cortex revealed by the infusion of zeta inhibitory pseudosubstrate.Frontiers in behavioral neuroscience · 2022Article
- GSK-3β activation is required for ZIP-induced disruption of learned fear.Scientific reports · 2020Article
- Article
- PKMζ Inhibition Disrupts Reconsolidation and Erases Object Recognition Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- In memoriam: John Lisman - commentaries on CaMKII as a memory molecule.Molecular brain · 2018Article
- What does LTP tell us about the roles of CaMKII and PKMζ in memory?Molecular brain · 2018Review
- Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.Molecular psychiatry · 2018Article
- Criteria for identifying the molecular basis of the engram (CaMKII, PKMzeta).Molecular brain · 2017Review
- Metaplasticity mechanisms restore plasticity and associativity in an animal model of Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Memory Retrieval Has a Dynamic Influence on the Maintenance Mechanisms That Are Sensitive to ζ-Inhibitory Peptide (ZIP).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Neuroscience: In search of the memory molecule.Nature · 2016Article
- Intrahippocampal Anisomycin Impairs Spatial Performance on the Morris Water Maze.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledProtein kinase M ζ (PKMζ), an atypical isoform of protein kinase C, has been suggested to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long-term memory (LTM). This evidence is heavily based on the use of ζ inhibitory peptide (ZIP), a supposed specific inhibitor of PKMζ that interferes with both LTP and LTM. Problematically, both LTP and LTM are unaffected in both constitutive and conditional PKMζ knock-out mice, yet both are still impaired by ZIP application, suggesting a nonspecific mechanism of action. Because translational interference can disrupt neural activity, we assessed network activity after a unilateral intrahippocampal infusion of ZIP in anesthetized rats. ZIP profoundly reduced spontaneous hippocampal local field potentials, comparable in magnitude to infusions of lidocaine, but with a slower onset and longer duration. Our results highlight a serious confound in interpreting the behavioral effects of ZIP. We suggest that future molecular approaches in neuroscience consider the intervening level of cellular and systems neurophysiology before claiming influences on behavior. SIGNIFICANCE STATEMENT: Long-term memory in the brain is thought to arise from a sustained molecular process that can maintain changes in synaptic plasticity. A so-called candidate for the title of "the memory molecule" is protein kinase M ζ (PKMζ), mainly because its inhibition by ζ inhibitory peptide (ZIP) interferes with previously established synaptic plasticity and memory. We show that brain applications of ZIP that can impair memory actually profoundly suppress spontaneous brain activity directly or can cause abnormal seizure activity. We suggest that normal brain activity occurring after learning may be a more primary element of memory permanence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.