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

Yuichiro Hayashi, Yoko Nabeshima, Katsunori Kobayashi, Tsuyoshi Miyakawa, Koichi Tanda, Keizo Takao, Hidenori Suzuki, Eisaku Esumi, Shigeru Noguchi, Yukiko Matsuda, Toshikuni Sasaoka, Tetsuo Noda, Jun Ichi Miyazaki, Masayoshi Mishina, Kazuo Funabiki, Yo Ichi Nabeshima

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg2+ block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus.

Original languageEnglish
Article number44
JournalMolecular brain
Volume7
Issue number1
DOIs
Publication statusPublished - 04-06-2014

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Dentate Gyrus
N-Methyl-D-Aspartate Receptors
Magnesium
Brain
Automatic Data Processing
Perforant Pathway
Parahippocampal Gyrus
Memory Disorders
Amino Acid Substitution
Short-Term Memory
Synapses
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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. In: Molecular brain. 2014 ; Vol. 7, No. 1.
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abstract = "Background: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg2+ block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus.",
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Hayashi, Y, Nabeshima, Y, Kobayashi, K, Miyakawa, T, Tanda, K, Takao, K, Suzuki, H, Esumi, E, Noguchi, S, Matsuda, Y, Sasaoka, T, Noda, T, Miyazaki, JI, Mishina, M, Funabiki, K & Nabeshima, YI 2014, 'Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus', Molecular brain, vol. 7, no. 1, 44. https://doi.org/10.1186/1756-6606-7-44

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.

In: Molecular brain, Vol. 7, No. 1, 44, 04.06.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus

AU - Hayashi, Yuichiro

AU - Nabeshima, Yoko

AU - Kobayashi, Katsunori

AU - Miyakawa, Tsuyoshi

AU - Tanda, Koichi

AU - Takao, Keizo

AU - Suzuki, Hidenori

AU - Esumi, Eisaku

AU - Noguchi, Shigeru

AU - Matsuda, Yukiko

AU - Sasaoka, Toshikuni

AU - Noda, Tetsuo

AU - Miyazaki, Jun Ichi

AU - Mishina, Masayoshi

AU - Funabiki, Kazuo

AU - Nabeshima, Yo Ichi

PY - 2014/6/4

Y1 - 2014/6/4

N2 - Background: Voltage-dependent block of the NMDA receptor by Mg2+ is thought to be central to the unique involvement of this receptor in higher brain functions. However, the in vivo role of the Mg2+ block in the mammalian brain has not yet been investigated, because brain-wide loss of the Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+ block in the dentate gyrus regulates hippocampal spatial information processing by attenuating activity-dependent synaptic potentiation in the dentate gyrus.

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