Cargando…

Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor

CaMK2N1 and CaMK2N2 are endogenous inhibitors of calcium/calmodulin-dependent protein kinase II (CaMKII), a key synaptic signaling molecule for learning and memory. Here, we investigated the learning and memory function of CaMK2N1 by knocking-down its expression in dorsal hippocampus of mice. We fou...

Descripción completa

Detalles Bibliográficos
Autores principales: Vigil, Fabio Antonio, Mizuno, Keiko, Lucchesi, Walter, Valls-Comamala, Victoria, Giese, Karl Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481336/
https://www.ncbi.nlm.nih.gov/pubmed/28642476
http://dx.doi.org/10.1038/s41598-017-04355-8
_version_ 1783245375532957696
author Vigil, Fabio Antonio
Mizuno, Keiko
Lucchesi, Walter
Valls-Comamala, Victoria
Giese, Karl Peter
author_facet Vigil, Fabio Antonio
Mizuno, Keiko
Lucchesi, Walter
Valls-Comamala, Victoria
Giese, Karl Peter
author_sort Vigil, Fabio Antonio
collection PubMed
description CaMK2N1 and CaMK2N2 are endogenous inhibitors of calcium/calmodulin-dependent protein kinase II (CaMKII), a key synaptic signaling molecule for learning and memory. Here, we investigated the learning and memory function of CaMK2N1 by knocking-down its expression in dorsal hippocampus of mice. We found that reduced CaMK2N1 expression does not affect contextual fear long-term memory (LTM) formation. However, we show that it impairs maintenance of established LTM, but only if retrieval occurs. CaMK2N1 knockdown prevents a decrease of threonine-286 (T286) autophosphorylation of αCaMKII and increases GluA1 levels in hippocampal synapses after retrieval of contextual fear LTM. CaMK2N1 knockdown can also increase CaMK2N2 expression, but we show that such increased expression does not affect LTM after retrieval. We also found that substantial overexpression of CaMK2N2 in dorsal hippocampus impairs LTM formation, but not LTM maintenance, suggesting that CaMKII activity is not required for LTM storage. Taken together, we propose a specific function for CaMK2N1; enabling LTM maintenance after retrieval by inhibiting T286 autophosphorylation of αCaMKII.
format Online
Article
Text
id pubmed-5481336
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-54813362017-06-26 Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor Vigil, Fabio Antonio Mizuno, Keiko Lucchesi, Walter Valls-Comamala, Victoria Giese, Karl Peter Sci Rep Article CaMK2N1 and CaMK2N2 are endogenous inhibitors of calcium/calmodulin-dependent protein kinase II (CaMKII), a key synaptic signaling molecule for learning and memory. Here, we investigated the learning and memory function of CaMK2N1 by knocking-down its expression in dorsal hippocampus of mice. We found that reduced CaMK2N1 expression does not affect contextual fear long-term memory (LTM) formation. However, we show that it impairs maintenance of established LTM, but only if retrieval occurs. CaMK2N1 knockdown prevents a decrease of threonine-286 (T286) autophosphorylation of αCaMKII and increases GluA1 levels in hippocampal synapses after retrieval of contextual fear LTM. CaMK2N1 knockdown can also increase CaMK2N2 expression, but we show that such increased expression does not affect LTM after retrieval. We also found that substantial overexpression of CaMK2N2 in dorsal hippocampus impairs LTM formation, but not LTM maintenance, suggesting that CaMKII activity is not required for LTM storage. Taken together, we propose a specific function for CaMK2N1; enabling LTM maintenance after retrieval by inhibiting T286 autophosphorylation of αCaMKII. Nature Publishing Group UK 2017-06-22 /pmc/articles/PMC5481336/ /pubmed/28642476 http://dx.doi.org/10.1038/s41598-017-04355-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Vigil, Fabio Antonio
Mizuno, Keiko
Lucchesi, Walter
Valls-Comamala, Victoria
Giese, Karl Peter
Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title_full Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title_fullStr Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title_full_unstemmed Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title_short Prevention of long-term memory loss after retrieval by an endogenous CaMKII inhibitor
title_sort prevention of long-term memory loss after retrieval by an endogenous camkii inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481336/
https://www.ncbi.nlm.nih.gov/pubmed/28642476
http://dx.doi.org/10.1038/s41598-017-04355-8
work_keys_str_mv AT vigilfabioantonio preventionoflongtermmemorylossafterretrievalbyanendogenouscamkiiinhibitor
AT mizunokeiko preventionoflongtermmemorylossafterretrievalbyanendogenouscamkiiinhibitor
AT lucchesiwalter preventionoflongtermmemorylossafterretrievalbyanendogenouscamkiiinhibitor
AT vallscomamalavictoria preventionoflongtermmemorylossafterretrievalbyanendogenouscamkiiinhibitor
AT giesekarlpeter preventionoflongtermmemorylossafterretrievalbyanendogenouscamkiiinhibitor