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Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation
Two-trial learning in Aplysia reveals nonlinear interactions between training trials: A single trial has no effect, but two precisely spaced trials induce long-term memory. Extracellularly regulated kinase (ERK) activity is essential for intertrial interactions, but the mechanism remains unresolved....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546540/ https://www.ncbi.nlm.nih.gov/pubmed/36161885 http://dx.doi.org/10.1073/pnas.2210478119 |
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author | Kukushkin, Nikolay V. Tabassum, Tasnim Carew, Thomas J. |
author_facet | Kukushkin, Nikolay V. Tabassum, Tasnim Carew, Thomas J. |
author_sort | Kukushkin, Nikolay V. |
collection | PubMed |
description | Two-trial learning in Aplysia reveals nonlinear interactions between training trials: A single trial has no effect, but two precisely spaced trials induce long-term memory. Extracellularly regulated kinase (ERK) activity is essential for intertrial interactions, but the mechanism remains unresolved. A combination of immunochemical and optogenetic tools reveals unexpected complexity of ERK signaling during the induction of long-term synaptic facilitation by two spaced pulses of serotonin (5-hydroxytryptamine, 5HT). Specifically, dual ERK phosphorylation at its activating TxY motif is accompanied by dephosphorylation at the pT position, leading to a buildup of inactive, singly phosphorylated pY-ERK. Phosphorylation and dephosphorylation occur concurrently but scale differently with varying 5HT concentrations, predicting that mixed two-trial protocols involving both “strong” and “weak” 5HT pulses should be sensitive to the precise order and timing of trials. Indeed, long-term synaptic facilitation is induced only when weak pulses precede strong, not vice versa. This may represent a physiological mechanism to prioritize memory of escalating threats. |
format | Online Article Text |
id | pubmed-9546540 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-95465402023-03-26 Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation Kukushkin, Nikolay V. Tabassum, Tasnim Carew, Thomas J. Proc Natl Acad Sci U S A Biological Sciences Two-trial learning in Aplysia reveals nonlinear interactions between training trials: A single trial has no effect, but two precisely spaced trials induce long-term memory. Extracellularly regulated kinase (ERK) activity is essential for intertrial interactions, but the mechanism remains unresolved. A combination of immunochemical and optogenetic tools reveals unexpected complexity of ERK signaling during the induction of long-term synaptic facilitation by two spaced pulses of serotonin (5-hydroxytryptamine, 5HT). Specifically, dual ERK phosphorylation at its activating TxY motif is accompanied by dephosphorylation at the pT position, leading to a buildup of inactive, singly phosphorylated pY-ERK. Phosphorylation and dephosphorylation occur concurrently but scale differently with varying 5HT concentrations, predicting that mixed two-trial protocols involving both “strong” and “weak” 5HT pulses should be sensitive to the precise order and timing of trials. Indeed, long-term synaptic facilitation is induced only when weak pulses precede strong, not vice versa. This may represent a physiological mechanism to prioritize memory of escalating threats. National Academy of Sciences 2022-09-26 2022-10-04 /pmc/articles/PMC9546540/ /pubmed/36161885 http://dx.doi.org/10.1073/pnas.2210478119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Kukushkin, Nikolay V. Tabassum, Tasnim Carew, Thomas J. Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title | Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title_full | Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title_fullStr | Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title_full_unstemmed | Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title_short | Precise timing of ERK phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
title_sort | precise timing of erk phosphorylation/dephosphorylation determines the outcome of trial repetition during long-term memory formation |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546540/ https://www.ncbi.nlm.nih.gov/pubmed/36161885 http://dx.doi.org/10.1073/pnas.2210478119 |
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