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Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol

Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation...

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Detalles Bibliográficos
Autores principales: Liu, Rong-Yu, Neveu, Curtis, Smolen, Paul, Cleary, Leonard J., Byrne, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473109/
https://www.ncbi.nlm.nih.gov/pubmed/28620076
http://dx.doi.org/10.1101/lm.044834.116
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author Liu, Rong-Yu
Neveu, Curtis
Smolen, Paul
Cleary, Leonard J.
Byrne, John H.
author_facet Liu, Rong-Yu
Neveu, Curtis
Smolen, Paul
Cleary, Leonard J.
Byrne, John H.
author_sort Liu, Rong-Yu
collection PubMed
description Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM). Previously, a computational model was developed which correctly predicted a novel enhanced training protocol that augmented LTF by searching for the protocol with maximal overlap of PKA and ERK activation. The present study focused on pharmacological approaches to enhance LTF. Combining an ERK activator, NSC, and a PKA activator, rolipram, enhanced LTF to a greater extent than did either drug alone. An even greater increase in LTF occurred when rolipram and NSC were combined with the Enhanced protocol. These results indicate superior memory can be achieved by enhanced protocols that take advantage of the structure and dynamics of the biochemical cascades underlying memory formation, used in conjunction with combinatorial pharmacology.
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spelling pubmed-54731092018-07-01 Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol Liu, Rong-Yu Neveu, Curtis Smolen, Paul Cleary, Leonard J. Byrne, John H. Learn Mem Research Developing treatment strategies to enhance memory is an important goal of neuroscience research. Activation of multiple biochemical signaling cascades, such as the protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways, is necessary to induce long-term synaptic facilitation (LTF), a correlate of long-term memory (LTM). Previously, a computational model was developed which correctly predicted a novel enhanced training protocol that augmented LTF by searching for the protocol with maximal overlap of PKA and ERK activation. The present study focused on pharmacological approaches to enhance LTF. Combining an ERK activator, NSC, and a PKA activator, rolipram, enhanced LTF to a greater extent than did either drug alone. An even greater increase in LTF occurred when rolipram and NSC were combined with the Enhanced protocol. These results indicate superior memory can be achieved by enhanced protocols that take advantage of the structure and dynamics of the biochemical cascades underlying memory formation, used in conjunction with combinatorial pharmacology. Cold Spring Harbor Laboratory Press 2017-07 /pmc/articles/PMC5473109/ /pubmed/28620076 http://dx.doi.org/10.1101/lm.044834.116 Text en © 2017 Liu et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Liu, Rong-Yu
Neveu, Curtis
Smolen, Paul
Cleary, Leonard J.
Byrne, John H.
Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title_full Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title_fullStr Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title_full_unstemmed Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title_short Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol
title_sort superior long-term synaptic memory induced by combining dual pharmacological activation of pka and erk with an enhanced training protocol
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473109/
https://www.ncbi.nlm.nih.gov/pubmed/28620076
http://dx.doi.org/10.1101/lm.044834.116
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