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Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus

BACKGROUND: Voltage-dependent block of the NMDA receptor by Mg(2+) is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg(2+) block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg(2+)...

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Autores principales: Hayashi, Yuichiro, Nabeshima, Yoko, Kobayashi, Katsunori, Miyakawa, Tsuyoshi, Tanda, Koichi, Takao, Keizo, Suzuki, Hidenori, Esumi, Eisaku, Noguchi, Shigeru, Matsuda, Yukiko, Sasaoka, Toshikuni, Noda, Tetsuo, Miyazaki, Jun-ichi, Mishina, Masayoshi, Funabiki, Kazuo, Nabeshima, Yo-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073519/
https://www.ncbi.nlm.nih.gov/pubmed/24893573
http://dx.doi.org/10.1186/1756-6606-7-44
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author Hayashi, Yuichiro
Nabeshima, Yoko
Kobayashi, Katsunori
Miyakawa, Tsuyoshi
Tanda, Koichi
Takao, Keizo
Suzuki, Hidenori
Esumi, Eisaku
Noguchi, Shigeru
Matsuda, Yukiko
Sasaoka, Toshikuni
Noda, Tetsuo
Miyazaki, Jun-ichi
Mishina, Masayoshi
Funabiki, Kazuo
Nabeshima, Yo-ichi
author_facet Hayashi, Yuichiro
Nabeshima, Yoko
Kobayashi, Katsunori
Miyakawa, Tsuyoshi
Tanda, Koichi
Takao, Keizo
Suzuki, Hidenori
Esumi, Eisaku
Noguchi, Shigeru
Matsuda, Yukiko
Sasaoka, Toshikuni
Noda, Tetsuo
Miyazaki, Jun-ichi
Mishina, Masayoshi
Funabiki, Kazuo
Nabeshima, Yo-ichi
author_sort Hayashi, Yuichiro
collection PubMed
description BACKGROUND: Voltage-dependent block of the NMDA receptor by Mg(2+) is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg(2+) block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg(2+) block causes perinatal lethality. In this study, we used a brain-region specific knock-in mouse expressing an NMDA receptor that is defective for the Mg(2+) block in order to test its role in neural information processing. RESULTS: We devised a method to induce a single amino acid substitution (N595Q) in the GluN2A subunit of the NMDA receptor, specifically in the hippocampal dentate gyrus in mice. This mutation reduced the Mg(2+) block at the medial perforant path–granule cell synapse and facilitated synaptic potentiation induced by high-frequency stimulation. The mutants had more stable hippocampal place fields in the CA1 than the controls did, and place representation showed lower sensitivity to visual differences. In addition, behavioral tests revealed that the mutants had a spatial working memory deficit. CONCLUSIONS: These results suggest that the Mg(2+) block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus.
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spelling pubmed-40735192014-06-28 Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus Hayashi, Yuichiro Nabeshima, Yoko Kobayashi, Katsunori Miyakawa, Tsuyoshi Tanda, Koichi Takao, Keizo Suzuki, Hidenori Esumi, Eisaku Noguchi, Shigeru Matsuda, Yukiko Sasaoka, Toshikuni Noda, Tetsuo Miyazaki, Jun-ichi Mishina, Masayoshi Funabiki, Kazuo Nabeshima, Yo-ichi Mol Brain Research BACKGROUND: Voltage-dependent block of the NMDA receptor by Mg(2+) is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg(2+) block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg(2+) block causes perinatal lethality. In this study, we used a brain-region specific knock-in mouse expressing an NMDA receptor that is defective for the Mg(2+) block in order to test its role in neural information processing. RESULTS: We devised a method to induce a single amino acid substitution (N595Q) in the GluN2A subunit of the NMDA receptor, specifically in the hippocampal dentate gyrus in mice. This mutation reduced the Mg(2+) block at the medial perforant path–granule cell synapse and facilitated synaptic potentiation induced by high-frequency stimulation. The mutants had more stable hippocampal place fields in the CA1 than the controls did, and place representation showed lower sensitivity to visual differences. In addition, behavioral tests revealed that the mutants had a spatial working memory deficit. CONCLUSIONS: These results suggest that the Mg(2+) block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus. BioMed Central 2014-06-04 /pmc/articles/PMC4073519/ /pubmed/24893573 http://dx.doi.org/10.1186/1756-6606-7-44 Text en Copyright © 2014 Hayashi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hayashi, Yuichiro
Nabeshima, Yoko
Kobayashi, Katsunori
Miyakawa, Tsuyoshi
Tanda, Koichi
Takao, Keizo
Suzuki, Hidenori
Esumi, Eisaku
Noguchi, Shigeru
Matsuda, Yukiko
Sasaoka, Toshikuni
Noda, Tetsuo
Miyazaki, Jun-ichi
Mishina, Masayoshi
Funabiki, Kazuo
Nabeshima, Yo-ichi
Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title_full Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title_fullStr Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title_full_unstemmed Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title_short Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus
title_sort enhanced stability of hippocampal place representation caused by reduced magnesium block of nmda receptors in the dentate gyrus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073519/
https://www.ncbi.nlm.nih.gov/pubmed/24893573
http://dx.doi.org/10.1186/1756-6606-7-44
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