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Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model

Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional...

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Autores principales: Smolen, Paul, Baxter, Douglas A., Byrne, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410876/
https://www.ncbi.nlm.nih.gov/pubmed/22876169
http://dx.doi.org/10.1371/journal.pcbi.1002620
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author Smolen, Paul
Baxter, Douglas A.
Byrne, John H.
author_facet Smolen, Paul
Baxter, Douglas A.
Byrne, John H.
author_sort Smolen, Paul
collection PubMed
description Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been “tagged” by a stimulus sufficient for LTP and learning can “capture” PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.
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spelling pubmed-34108762012-08-08 Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model Smolen, Paul Baxter, Douglas A. Byrne, John H. PLoS Comput Biol Research Article Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been “tagged” by a stimulus sufficient for LTP and learning can “capture” PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance. Public Library of Science 2012-08-02 /pmc/articles/PMC3410876/ /pubmed/22876169 http://dx.doi.org/10.1371/journal.pcbi.1002620 Text en Smolen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Smolen, Paul
Baxter, Douglas A.
Byrne, John H.
Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title_full Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title_fullStr Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title_full_unstemmed Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title_short Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
title_sort molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410876/
https://www.ncbi.nlm.nih.gov/pubmed/22876169
http://dx.doi.org/10.1371/journal.pcbi.1002620
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