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Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse

Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) is a key mediator of activity-dependent neuronal modifications and has been implicated in the molecular mechanisms of learning and memory. Indeed, several types of CaMKIIα knock-in (KI) and knock-out (KO) mice revealed impairments in hippocamp...

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Autores principales: Yamagata, Yoko, Yanagawa, Yuchio, Imoto, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140109/
https://www.ncbi.nlm.nih.gov/pubmed/30225347
http://dx.doi.org/10.1523/ENEURO.0133-18.2018
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author Yamagata, Yoko
Yanagawa, Yuchio
Imoto, Keiji
author_facet Yamagata, Yoko
Yanagawa, Yuchio
Imoto, Keiji
author_sort Yamagata, Yoko
collection PubMed
description Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) is a key mediator of activity-dependent neuronal modifications and has been implicated in the molecular mechanisms of learning and memory. Indeed, several types of CaMKIIα knock-in (KI) and knock-out (KO) mice revealed impairments in hippocampal synaptic plasticity and behavioral learning. On the other hand, a similar role for CaMKIIα has been implicated in amygdala-dependent memory, but detailed analyses have not much been performed yet. To better understand its involvement in amygdala-dependent memory as compared to hippocampus-dependent memory, here we performed biochemical analyses and behavioral memory tests using the kinase-dead CaMKIIα (K42R)-KI mouse. In the Morris water maze tasks, homozygous mutants performed well in the visible platform trials, while they failed to form spatial memory in the hippocampus-dependent hidden platform trials. In fear conditioning, these mice were impaired but showed a certain level of amygdala-dependent cued fear memory, which lasted four weeks, while they showed virtually no hippocampus-dependent context discrimination. Neither stronger stimulation nor repetitive stimulation compensated for their memory deficits. The differential outcome of hippocampus- and amygdala-dependent memory in the mutant mouse was not due to differential expression of CaMKIIα between the hippocampus and the amygdala, because biochemical analyses revealed that both kinase activity and protein levels of CaMKII were indistinguishable between the two brain regions. These results indicate that kinase activity of CaMKIIα is indispensable for hippocampus-dependent memory, but not necessarily for amygdala-dependent memory. There may be a secondary, CaMKIIα activity-independent pathway, in addition to the CaMKIIα activity-dependent pathway, in the acquisition of amygdala-dependent memory.
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spelling pubmed-61401092018-09-17 Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse Yamagata, Yoko Yanagawa, Yuchio Imoto, Keiji eNeuro New Research Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) is a key mediator of activity-dependent neuronal modifications and has been implicated in the molecular mechanisms of learning and memory. Indeed, several types of CaMKIIα knock-in (KI) and knock-out (KO) mice revealed impairments in hippocampal synaptic plasticity and behavioral learning. On the other hand, a similar role for CaMKIIα has been implicated in amygdala-dependent memory, but detailed analyses have not much been performed yet. To better understand its involvement in amygdala-dependent memory as compared to hippocampus-dependent memory, here we performed biochemical analyses and behavioral memory tests using the kinase-dead CaMKIIα (K42R)-KI mouse. In the Morris water maze tasks, homozygous mutants performed well in the visible platform trials, while they failed to form spatial memory in the hippocampus-dependent hidden platform trials. In fear conditioning, these mice were impaired but showed a certain level of amygdala-dependent cued fear memory, which lasted four weeks, while they showed virtually no hippocampus-dependent context discrimination. Neither stronger stimulation nor repetitive stimulation compensated for their memory deficits. The differential outcome of hippocampus- and amygdala-dependent memory in the mutant mouse was not due to differential expression of CaMKIIα between the hippocampus and the amygdala, because biochemical analyses revealed that both kinase activity and protein levels of CaMKII were indistinguishable between the two brain regions. These results indicate that kinase activity of CaMKIIα is indispensable for hippocampus-dependent memory, but not necessarily for amygdala-dependent memory. There may be a secondary, CaMKIIα activity-independent pathway, in addition to the CaMKIIα activity-dependent pathway, in the acquisition of amygdala-dependent memory. Society for Neuroscience 2018-08-21 /pmc/articles/PMC6140109/ /pubmed/30225347 http://dx.doi.org/10.1523/ENEURO.0133-18.2018 Text en Copyright © 2018 Yamagata et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Yamagata, Yoko
Yanagawa, Yuchio
Imoto, Keiji
Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title_full Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title_fullStr Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title_full_unstemmed Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title_short Differential Involvement of Kinase Activity of Ca(2+)/Calmodulin-Dependent Protein Kinase IIα in Hippocampus- and Amygdala-Dependent Memory Revealed by Kinase-Dead Knock-In Mouse
title_sort differential involvement of kinase activity of ca(2+)/calmodulin-dependent protein kinase iiα in hippocampus- and amygdala-dependent memory revealed by kinase-dead knock-in mouse
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140109/
https://www.ncbi.nlm.nih.gov/pubmed/30225347
http://dx.doi.org/10.1523/ENEURO.0133-18.2018
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