title: Enhanced stability of hippocampal place representation caused by reduced magnesium block of NMDA receptors in the dentate gyrus.
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.
authors.affiliation: Horizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. yhayashi@obi.or.jp.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanda
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Eisaku
authors.initials: E
authors.lastname: Esumi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshikuni
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
authors.forename: Kazuo
authors.initials: K
authors.lastname: Funabiki
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Nabeshima
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018390:Gene Targeting; D019426:Integrases / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019426:Integrases; D008274:Magnesium; D050505:Mutant Proteins; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; C045073:Cre recombinase