Analysis of neuronal functions in mice lacking the NMDA receptor ε 1 subunit

Yoshiaki Miyamoto, Toshitaka Nabeshima

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

The NMDA subtype of glutamate receptor (GluR) plays an important role in excitatory neurotransmission, synaptic plasticity, brain development, and neurodegeneration. NMDA receptors are inherent high Ca2+-permeable channels, which are formed by heteromeric assembly of the GluRθ1 subunit (NR1) and any one of four GluRε subunits (GluRε 1-4; NR2A-D). Mice lacking the GluRε 1 subunit exhibited a malfunction of NMDA receptors, as evidenced by reduction of NMDA receptor channel current, hippocampal long-term potentiation, [3MK-801 binding, and NMDA-stimulated 45Ca2+ uptake. A biochemical analysis revealed a hyperfunction of dopaminergic and serotonergic neuronal systems in the frontal cortex and striatum of GluRε 1 mutant mice. The enhancement of dopaminergic neuronal activity in the striatum, at least, due to the disinhibition of inhibitory GABAergic neuronal input. GluRε 1 mutant mice showed an increase of locomotor activity in a novel environment attributed to the hyperfunction of the dopaminergic neuronal system, and an impairment of spatial, contextual, and latent learning. These findings provide evidence that NMDA receptors regulate behavior through the modulation of not only glutamatergic but also GABAergic and dopaminergic neuronal systems. Moreover, it is suggested that GluRe 1 mutant mice are useful as an animal model, which is associated with the malfunction of NMDA receptors and hyperfunction of the dopaminergic neuronal system.

Original languageEnglish
Pages (from-to)327-335
Number of pages9
JournalFolia Pharmacologica Japonica
Volume119
Issue number6
DOIs
Publication statusPublished - 18-07-2002
Externally publishedYes

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Glutamate Receptors
N-Methyl-D-Aspartate Receptors
N-Methylaspartate
Neuronal Plasticity
Long-Term Potentiation
Frontal Lobe
Locomotion
Synaptic Transmission
Animal Models
Learning
Brain

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Analysis of neuronal functions in mice lacking the NMDA receptor ε 1 subunit",
abstract = "The NMDA subtype of glutamate receptor (GluR) plays an important role in excitatory neurotransmission, synaptic plasticity, brain development, and neurodegeneration. NMDA receptors are inherent high Ca2+-permeable channels, which are formed by heteromeric assembly of the GluRθ1 subunit (NR1) and any one of four GluRε subunits (GluRε 1-4; NR2A-D). Mice lacking the GluRε 1 subunit exhibited a malfunction of NMDA receptors, as evidenced by reduction of NMDA receptor channel current, hippocampal long-term potentiation, [3MK-801 binding, and NMDA-stimulated 45Ca2+ uptake. A biochemical analysis revealed a hyperfunction of dopaminergic and serotonergic neuronal systems in the frontal cortex and striatum of GluRε 1 mutant mice. The enhancement of dopaminergic neuronal activity in the striatum, at least, due to the disinhibition of inhibitory GABAergic neuronal input. GluRε 1 mutant mice showed an increase of locomotor activity in a novel environment attributed to the hyperfunction of the dopaminergic neuronal system, and an impairment of spatial, contextual, and latent learning. These findings provide evidence that NMDA receptors regulate behavior through the modulation of not only glutamatergic but also GABAergic and dopaminergic neuronal systems. Moreover, it is suggested that GluRe 1 mutant mice are useful as an animal model, which is associated with the malfunction of NMDA receptors and hyperfunction of the dopaminergic neuronal system.",
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Analysis of neuronal functions in mice lacking the NMDA receptor ε 1 subunit. / Miyamoto, Yoshiaki; Nabeshima, Toshitaka.

In: Folia Pharmacologica Japonica, Vol. 119, No. 6, 18.07.2002, p. 327-335.

Research output: Contribution to journalReview article

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