ArticleBMC systems biology2010
The protein kinase Mζ network as a bistable switch to store neuronal memory.
Article in BMC systems biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Maintenance of memory by negative-feedback of synaptic protein elimination: Modeling KIBRA-bioRxiv : the preprint server for biology · 2025Article
- A Modeling and Machine Learning Pipeline to Rationally Design Treatments to Restore Neuroendocrine Disorders in Heterogeneous Individuals.Frontiers in genetics · 2021Article
- Robustness and parameter geography in post-translational modification systems.PLoS computational biology · 2020Article
- From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.Seminars in cell & developmental biology · 2019Review
- Experiments with Snails Add to Our Knowledge about the Role of aPKC Subfamily Kinases in Learning.International journal of molecular sciences · 2019Article
- Coupled feedback loops maintain synaptic long-term potentiation: A computational model of PKMzeta synthesis and AMPA receptor trafficking.PLoS computational biology · 2018Article
- Computational model of a positive BDNF feedback loop in hippocampal neurons following inhibitory avoidance training.Learning & memory (Cold Spring Harbor, N.Y.) · 2016Article
- Computational principles of memory.Nature neuroscience · 2016Review
- Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches.Cell systems · 2016Article
- Information Compression, Multiple Alignment, and the Representation and Processing of Knowledge in the Brain.Frontiers in psychology · 2016Article
- Atypical PKCs in memory maintenance: the roles of feedback and redundancy.Learning & memory (Cold Spring Harbor, N.Y.) · 2015Article
- Maintenance of memory by negative feedback of synaptic protein elimination: modeling KIBRA-PKMζ dynamics in LTP.Learning & memory (Cold Spring Harbor, N.Y.)Article
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2 authors.
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Abstract
backgroundProtein kinase Mζ (PKMζ), the brain-specific, atypical protein kinase C isoform, plays a key role in long-term maintenance of memory. This molecule is essential for long-term potentiation of the neuron and various modalities of learning such as spatial memory and fear conditioning. It is unknown, however, how PKMζ stores information for long periods of time despite molecular turnover.
resultsWe hypothesized that PKMζ forms a bistable switch because it appears to constitute a positive feedback loop (PKMζ induces its local synthesis) part of which is ultrasensitive (PKMζ stimulates its synthesis through dual pathways). To examine this hypothesis, we modeled the biochemical network of PKMζ with realistic kinetic parameters. Bifurcation analyses of the model showed that the system maintains either the up state or the down state according to previous inputs. Furthermore, the model was able to reproduce a variety of previous experimental results regarding synaptic plasticity and learning, which suggested that it captures the essential mechanism for neuronal memory. We proposed in vitro and in vivo experiments that would critically examine the validity of the model and illuminate the pivotal role of PKMζ in synaptic plasticity and learning.
conclusionsThis study revealed bistability of the PKMζ network and supported its pivotal role in long-term storage of memory.
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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.