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Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation
BACKGROUND: The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediat...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663561/ https://www.ncbi.nlm.nih.gov/pubmed/19265511 http://dx.doi.org/10.1186/1756-6606-2-7 |
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author | Inoue, Naoko Nakao, Harumi Migishima, Rika Hino, Toshiaki Matsui, Minoru Hayashi, Fumihiko Nakao, Kazuki Manabe, Toshiya Aiba, Atsu Inokuchi, Kaoru |
author_facet | Inoue, Naoko Nakao, Harumi Migishima, Rika Hino, Toshiaki Matsui, Minoru Hayashi, Fumihiko Nakao, Kazuki Manabe, Toshiya Aiba, Atsu Inokuchi, Kaoru |
author_sort | Inoue, Naoko |
collection | PubMed |
description | BACKGROUND: The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP(3 )receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice. RESULTS: In this study, we generated short-form-specific gene targeting (KO) mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice. CONCLUSION: These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation. |
format | Text |
id | pubmed-2663561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26635612009-04-01 Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation Inoue, Naoko Nakao, Harumi Migishima, Rika Hino, Toshiaki Matsui, Minoru Hayashi, Fumihiko Nakao, Kazuki Manabe, Toshiya Aiba, Atsu Inokuchi, Kaoru Mol Brain Research BACKGROUND: The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP(3 )receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice. RESULTS: In this study, we generated short-form-specific gene targeting (KO) mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice. CONCLUSION: These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation. BioMed Central 2009-03-05 /pmc/articles/PMC2663561/ /pubmed/19265511 http://dx.doi.org/10.1186/1756-6606-2-7 Text en Copyright © 2009 Inoue et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Inoue, Naoko Nakao, Harumi Migishima, Rika Hino, Toshiaki Matsui, Minoru Hayashi, Fumihiko Nakao, Kazuki Manabe, Toshiya Aiba, Atsu Inokuchi, Kaoru Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title | Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title_full | Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title_fullStr | Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title_full_unstemmed | Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title_short | Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation |
title_sort | requirement of the immediate early gene vesl-1s/homer-1a for fear memory formation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663561/ https://www.ncbi.nlm.nih.gov/pubmed/19265511 http://dx.doi.org/10.1186/1756-6606-2-7 |
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