The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
Chapter 2 PKMζ, LTP maintenance, and the dynamic molecular biology of memory storage
Abstract
How memories persist is a fundamental neurobiological question. The most commonly studied physiological model of memory is long-term potentiation (LTP). The molecular mechanisms of LTP can be divided into two phases: induction, triggering the potentiation; and maintenance, sustaining the potentiation over time. Although many molecules participate in induction, very few have been implicated in the mechanism of maintenance. Understanding maintenance, however, is critical for testing the hypothesis that LTP sustains memory storage in the brain. Only a single molecule has been found both necessary and sufficient for maintaining LTP--the brain-specific, atypical PKC isoform, protein kinase Mzeta (PKMzeta). Although full-length PKC isoforms respond to transient second messengers, and are involved in LTP induction, PKMzeta is a second messenger-independent kinase, consisting of the independent catalytic domain of PKCzeta, and is persistently active to sustain LTP maintenance. PKMzeta is produced by a unique PKMzeta mRNA, which is generated by an internal promoter within the PKCzeta gene and transported to the dendrites of neurons. LTP induction increases new PKMzeta synthesis, and the increased level of PKMzeta then enhances synaptic transmission by doubling the number of postsynaptic AMPA receptors (AMPAR) through GluR2 subunit-mediated trafficking of the receptors to the synapse. PKMzeta mediates synaptic potentiation specifically during the late-phase of LTP, as PKMzeta inhibitors can reverse established LTP when applied several hours after tetanization in hippocampal slices or 1 day after tetanization in vivo. These studies set the stage for testing the hypothesis that the mechanism of LTP maintenance sustains memory storage. PKMzeta inhibition in the hippocampus after learning eliminates the retention of spatial memory. Once the PKMzeta inhibitor has been eliminated, the memory is still erased, but new spatial memories can be learned and stored. Similar results are found for conditioned taste aversion when the inhibitor is injected in the insular neocortex. Thus PKMzeta is the first molecule found to be a component of the long-term memory trace.
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“PKA, CaMKIV, protein kinase M-z, and extracellular signal -regulated kinase (ERK), as well as other signaling molecules, initiate protein synthesis either locally in the dendrites from prefabricated mRNA or by nuclear transcription (Sacktor 2008).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Sacktor 2008
In the citing paper
“The latter involves interactions with transcription factors, including cAMP response element -binding protein (CREB).”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Sacktor 2008
In the citing paper
“Not only does long-term plasticity cause structural changes in synapses, but the maintenance of the change in synaptic strength during LTP is protein synthesis -dependent.”
From NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012) · cites this paper as Sacktor 2008
In the citing paper
“several studies have shown that the kinase PKMζ is engaged at ≥1 h after induction and then contributes to maintenance of LTP (39).”
From Synaptic evidence for the efficacy of spaced learning (2012) · cites this paper as [39]
Citations
Cites
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“How does newly synthesized PKMz affect only specific, activated synapses? One possibility is that the kinase might be involved in the process of synaptic tagging and capture (Sossin, 1996; Frey and Morris, 1997; Sajikumar et al., 2005).”
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Storage of spatial information by the maintenance mechanism of LTP
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Self-citation
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Lernen, Gedächtnis, prägende Erfahrung
Müller, W. D. A., & Frings, S. (2009) · Springer-Lehrbuch · doi:10.1007/978-3-642-00462-9_24
PKMζ drives spatial memory reconsolidation but not maintenance
de Oliveira, J. R., Rossato, J. I., Souza, J., Orvate, R., Carneiro, L., Baracho, A. L., & Cammarota, M. (2025) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2025.1638371
Vingan, I., Phatarpekar, S., Tung, V. S. K., Hernandez, A. I., Evgrafov, O. V., & Alarcón, J. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.22.677884
Dosage effect of copy number variation in epilepsy and ten regions of the human brain
De, T., Coin, L., & Johnson, M. R. (2025) · Scientific Reports · doi:10.1038/s41598-025-28338-2
Transcriptomic signatures of hippocampal active place avoidance memory maintenance
Vingan, I., Phatarpekar, S., Tung, V. S. K., Hernandez, A. I., Evgrafov, O. V., & Alarcón, J. M. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1769317
The how and why for multiple forms of hippocampal LTP
Gall, C. M., Le, A. A., & LYNCH, G. S. (2026) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2026.1855059
Synaptic plasticity processes underlying consolidation and reconsolidation of Pavlovian conditioning
Rigby, P. T. (2012) · The University of Bath Online Publications Store (The University of Bath)
Spinal Sensitization Mechanisms Promoting Pain: Gabaergic Disinhibition and Pkmζ-Mediated Plasticity
Asiedu, M. N. (2012) · UA Campus Repository (The University of Arizona)
Metadata
- Authors
- Sacktor, T. C.
- Affiliations
- State University of New York (US)
- Corresponding author
- Sacktor, Todd Charlton
- Venue
- Progress in Brain Research
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 169
- Pages
- 27-40
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W1550519555
- Cited by
- 208
- References
- 86
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 14 · 2014: 17 · 2013: 25 · 2012: 24
- FWCI
- 29.63
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- PKMzeta, long-term potentiation, LTP maintenance, memory storage, protein kinase C zeta, dendritic mRNA transport, AMPA receptor trafficking, GluR2 subunit, synaptic potentiation, late-phase LTP, spatial memory, conditioned taste aversion, hippocampus, memory traces
- MeSH terms
- Animals, Hippocampus, Humans, Memory, Molecular Biology, Protein Kinase C, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Rats
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