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 language | English |
|---|---|
| Article number | 44 |
| Journal | Molecular Brain |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 04-06-2014 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cellular and Molecular Neuroscience
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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 journal › Article
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.
AB - 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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U2 - 10.1186/1756-6606-7-44
DO - 10.1186/1756-6606-7-44
M3 - Article
VL - 7
JO - Molecular Brain
JF - Molecular Brain
SN - 1756-6606
IS - 1
M1 - 44
ER -