Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783355558486605824 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6140109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT yamagatayoko differentialinvolvementofkinaseactivityofca2calmodulindependentproteinkinaseiiainhippocampusandamygdaladependentmemoryrevealedbykinasedeadknockinmouse AT yanagawayuchio differentialinvolvementofkinaseactivityofca2calmodulindependentproteinkinaseiiainhippocampusandamygdaladependentmemoryrevealedbykinasedeadknockinmouse AT imotokeiji differentialinvolvementofkinaseactivityofca2calmodulindependentproteinkinaseiiainhippocampusandamygdaladependentmemoryrevealedbykinasedeadknockinmouse |