ArticlePLoS computational biology2018
Coupled feedback loops maintain synaptic long-term potentiation: A computational model of PKMzeta synthesis and AMPA receptor trafficking.
Article in PLoS computational biology, 2018. 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.
- Environment Enrichment Facilitates Long-Term Memory Consolidation through Behavioral Tagging.eNeuro · 2023Article
- Karim Nader and the unification of memory erasure: PKMζ inhibition and reconsolidation blockade.Brain research bulletin · 2023Review
- Distinctive properties of biological neural networks and recent advances in bottom-up approaches toward a better biologically plausible neural network.Frontiers in computational neuroscience · 2023Review
- Article
- Persistent increases of PKMζ in memory-activated neurons trace LTP maintenance during spatial long-term memory storage.The European journal of neuroscience · 2021Article
- Modeling suggests combined-drug treatments for disorders impairing synaptic plasticity via shared signaling pathways.Journal of computational neuroscience · 2021Article
- Blockade of BDNF signalling attenuates chronic visceral hypersensitivity in an IBS-like rat model.European journal of pain (London, England) · 2020Article
- Effects of Exercise on Long-Term Potentiation in Neuropsychiatric Disorders.Advances in experimental medicine and biology · 2020Review
- Comparing Theories for the Maintenance of Late LTP and Long-Term Memory: Computational Analysis of the Roles of Kinase Feedback Pathways and Synaptic Reactivation.Frontiers in computational neuroscience · 2020Article
- From membrane receptors to protein synthesis and actin cytoskeleton: Mechanisms underlying long lasting forms of synaptic plasticity.Seminars in cell & developmental biology · 2019Review
- aPKC in neuronal differentiation, maturation and function.Neuronal signaling · 2019Review
- How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory.Learning & memory (Cold Spring Harbor, N.Y.) · 2019Review
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Authors and funding
2 authors.
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Abstract
In long-term potentiation (LTP), one of the most studied types of neural plasticity, synaptic strength is persistently increased in response to stimulation. Although a number of different proteins have been implicated in the sub-cellular molecular processes underlying induction and maintenance of LTP, the precise mechanisms remain unknown. A particular challenge is to demonstrate that a proposed molecular mechanism can provide the level of stability needed to maintain memories for months or longer, in spite of the fact that many of the participating molecules have much shorter life spans. Here we present a computational model that combines simulations of several biochemical reactions that have been suggested in the LTP literature and show that the resulting system does exhibit the required stability. At the core of the model are two interlinked feedback loops of molecular reactions, one involving the atypical protein kinase PKMζ and its messenger RNA, the other involving PKMζ and GluA2-containing AMPA receptors. We demonstrate that robust bistability-stable equilibria both in the synapse's potentiated and unpotentiated states-can arise from a set of simple molecular reactions. The model is able to account for a wide range of empirical results, including induction and maintenance of late-phase LTP, cellular memory reconsolidation and the effects of different pharmaceutical interventions.
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