Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Inoue, Naoko, Nakao, Harumi, Migishima, Rika, Hino, Toshiaki, Matsui, Minoru, Hayashi, Fumihiko, Nakao, Kazuki, Manabe, Toshiya, Aiba, Atsu, Inokuchi, Kaoru
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
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
_version_ 1782165908366557184
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
work_keys_str_mv AT inouenaoko requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT nakaoharumi requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT migishimarika requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT hinotoshiaki requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT matsuiminoru requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT hayashifumihiko requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT nakaokazuki requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT manabetoshiya requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT aibaatsu requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation
AT inokuchikaoru requirementoftheimmediateearlygenevesl1shomer1aforfearmemoryformation