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

• MIYAMOTO Yoshiaki

  Department of Molecular Genetics, National Institute for Longevity Sciences

• NABESHIMA Toshitaka

  Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine

Bibliographic Information

Other Title

• ＮＭＤＡ受容体ＧｌｕＲε１サブユニット欠損マウスにおける神経機能解析
• テーシス NMDA受容体GluRε1サブユニット欠損マウスにおける神経機能解析
• テーシス NMDA ジュヨウタイ GluR イプシロン 1 サブユニット ケッソン マウス ニ オケル シンケイ キノウ カイセキ

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 GluRζ1 subunit (NR1) and any one of four GluRε subunits (GluRε1-4; NR2A-D). Mice lacking the GluRε1 subunit exhibited a malfunction of NMDA receptors, as evidenced by reduction of NMDA receptor channel current, hippocampal long-term potentiation, [³H]MK-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 GluRε1 mutant mice. The enhancement of dopaminergic neuronal activity in the striatum, at least, due to the disinhibition of inhibitory GABAergic neuronal input. GluRε1 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 GluRε1 mutant mice are useful as an animal model, which is associated with the malfunction of NMDA receptors and hyperfunction of the dopaminergic neuronal system.<br>

Journal

• Folia Pharmacologica Japonica

  Folia Pharmacologica Japonica 119 (6), 327-335, 2002

  The Japanese Pharmacological Society

Keywords

• NMDA receptor
• GluR1 subunit
• dopaminergic neuronal system
• hyperlocomotion
• learning and memory

Details

• CRID: 1390001204273692672
• NII Article ID: 10008992225
• NII Book ID: AN00198335
• DOI: 10.1254/fpj.119.327
• COI: 1:STN:280:DC%2BD38zkslSnug%3D%3D
• ISSN: 13478397
• ISSN: 00155691
• NDL BIB ID: 6239638
• PubMed: 12089904
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6239638
• Web Site: https://search.jamas.or.jp/link/ui/2002236916
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed