{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1390001204273692672.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1254/fpj.119.327"}},{"identifier":{"@type":"COI","@value":"1:STN:280:DC%2BD38zkslSnug%3D%3D"}},{"identifier":{"@type":"PMID","@value":"12089904"}},{"identifier":{"@type":"NDL_BIB_ID","@value":"6239638"}},{"identifier":{"@type":"URI","@value":"http://id.ndl.go.jp/bib/6239638"}},{"identifier":{"@type":"URI","@value":"https://ndlsearch.ndl.go.jp/books/R000000004-I6239638"}},{"identifier":{"@type":"NAID","@value":"10008992225"}},{"identifier":{"@type":"URI","@value":"https://search.jamas.or.jp/link/ui/2002236916"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Analysis of neuronal functions in mice lacking the NMDA receptor .EPSILON.1 subunit."},{"@language":"ja","@value":"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"},{"@value":"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"},{"@language":"ja-Kana","@value":"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"}],"dc:language":"ja","description":[{"type":"abstract","notation":[{"@language":"en","@value":"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 Ca<sup>2+</sup>-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, [<sup>3</sup>H]MK-801 binding, and NMDA-stimulated <sup>45</sup>Ca<sup>2+</sup> 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>"},{"@language":"ja","@value":"NMDA型グルタミン酸受容体は，中枢神経系における興奮性シナプス伝達，シナプス可塑性，神経発達および神経変性など種々の神経活動において，重要な役割を担っている．NMDA受容体は，高いCa<sup>2+</sup>透過性を有したイオンチャネルを内蔵しており，GluRζ1（NR1）サブユニットおよび4種類のGluRε1-4（NR2A-D）サブユニットによってヘテロ複合体として形成されている．標的遺伝子改変法によりGluRε1サブユニットを欠損させたマウスでは，海馬CA1領域でのNMDA受容体依存性シナプス電流や長期増強（LTP）の誘導，前脳での非競合的NMDA受容体アンタゴニスト[<sup>3</sup>H]MK-801の特異的結合量およびNMDA受容体を介する<sup>45</sup>Ca<sup>2+</sup>取り込み量が低下しており，NMDA受容体の機能低下を示した．GluRε1欠損マウスの前頭皮質および線条体においては，ドパミンおよびセロトニンの代謝回転の亢進が観察され，ドパミンおよびセロトニン作動性神経系の機能亢進を示した．この線条体におけるドパミン作動性神経系の機能亢進は，NMDA受容体の機能低下によって，ドパミン作動性神経系に対するGABA作動性神経系の抑制機能が低下することが原因であった．また，GluRε1欠損マウスでは，ドパミン作動性神経系の機能亢進による新奇環境下での運動過多が観察された．さらに，モーリス水迷路試験，恐怖条件付け試験および水探索試験において，それぞれ空間，文脈および潜在学習などの記憶·学習機能の低下が観察された．以上のことから，NMDA受容体がグルタミン酸作動性神経系のみならず，間接的にGABA作動性神経系やドパミン作動性神経系を調節することによって，各種の行動変化をもたらすことが示唆された．また，GluRε1欠損マウスが，NMDA受容体の機能低下とドパミン作動性神経系の機能亢進に関連する精神分裂病の新たなモデル動物となりえることが示唆された．<br>"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420564276165759616","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"70076751"},{"@type":"NRID","@value":"1000070076751"},{"@type":"CINII_AUTHOR_ID","@value":"DA06105941"},{"@type":"URI","@value":"https://ci.nii.ac.jp/author/DA06105941#entity"},{"@type":"URI","@value":"https://viaf.org/viaf/NII%7CDA06105941"},{"@type":"NRID","@value":"9000003105277"},{"@type":"NRID","@value":"9000002275479"},{"@type":"NRID","@value":"9000005214494"},{"@type":"NRID","@value":"9000021366072"},{"@type":"NRID","@value":"9000021360466"},{"@type":"NRID","@value":"9000021309191"},{"@type":"NRID","@value":"9000365513033"},{"@type":"NRID","@value":"9000365513025"},{"@type":"NRID","@value":"9000410156310"},{"@type":"NRID","@value":"9000000274162"},{"@type":"NRID","@value":"9000000612940"},{"@type":"NRID","@value":"9000002866973"},{"@type":"NRID","@value":"9000005221902"},{"@type":"NRID","@value":"9000021248243"},{"@type":"NRID","@value":"9000325816614"},{"@type":"NRID","@value":"9000019147041"},{"@type":"NRID","@value":"9000254682696"},{"@type":"NRID","@value":"9000021382967"},{"@type":"NRID","@value":"9000021216532"},{"@type":"NRID","@value":"9000020394921"},{"@type":"NRID","@value":"9000411832479"},{"@type":"NRID","@value":"9000255839956"},{"@type":"NRID","@value":"9000256479928"},{"@type":"NRID","@value":"9000023354166"},{"@type":"NRID","@value":"9000021366080"},{"@type":"NRID","@value":"9000021217466"},{"@type":"NRID","@value":"9000380967299"},{"@type":"NRID","@value":"9000253213706"},{"@type":"NRID","@value":"9000253212584"},{"@type":"NRID","@value":"9000410161725"},{"@type":"NRID","@value":"9000392651184"},{"@type":"NRID","@value":"9000016937478"},{"@type":"NRID","@value":"9000021401309"},{"@type":"NRID","@value":"9000021810268"},{"@type":"NRID","@value":"9000256474446"},{"@type":"NRID","@value":"9000257985031"},{"@type":"NRID","@value":"9000363365931"},{"@type":"NRID","@value":"9000021218903"},{"@type":"NRID","@value":"9000020004170"},{"@type":"NRID","@value":"9000404821586"},{"@type":"NRID","@value":"9000275821403"},{"@type":"NRID","@value":"9000253213937"},{"@type":"NRID","@value":"9000410175381"},{"@type":"NRID","@value":"9000238294953"},{"@type":"NRID","@value":"9000021314138"},{"@type":"NRID","@value":"9000021336275"},{"@type":"NRID","@value":"9000020266884"},{"@type":"NRID","@value":"9000255840695"},{"@type":"NRID","@value":"9000415345068"},{"@type":"NRID","@value":"9000003088570"},{"@type":"NRID","@value":"9000256472200"},{"@type":"NRID","@value":"9000004254446"},{"@type":"NRID","@value":"9000254215941"},{"@type":"NRID","@value":"9000283796423"},{"@type":"NRID","@value":"9000256474712"},{"@type":"NRID","@value":"9000411836660"},{"@type":"NRID","@value":"9000016808229"},{"@type":"NRID","@value":"9000363365925"},{"@type":"NRID","@value":"9000021441053"},{"@type":"NRID","@value":"9000396113820"},{"@type":"NRID","@value":"9000020409830"},{"@type":"NRID","@value":"9000021383414"},{"@type":"NRID","@value":"9000021401154"},{"@type":"NRID","@value":"9000255842150"},{"@type":"NRID","@value":"9000005227862"},{"@type":"NRID","@value":"9000360556367"},{"@type":"NRID","@value":"9000253020832"},{"@type":"NRID","@value":"9000258051871"},{"@type":"NRID","@value":"9000000967274"},{"@type":"NRID","@value":"9000254682095"},{"@type":"NRID","@value":"9000023360493"},{"@type":"NRID","@value":"9000383202592"},{"@type":"NRID","@value":"9000253520326"},{"@type":"NRID","@value":"9000248215973"},{"@type":"NRID","@value":"9000254683077"},{"@type":"NRID","@value":"9000311506112"},{"@type":"NRID","@value":"9000256472018"},{"@type":"NRID","@value":"9000016970339"},{"@type":"NRID","@value":"9000000967514"},{"@type":"NRID","@value":"9000002867463"},{"@type":"NRID","@value":"9000020760116"},{"@type":"NRID","@value":"9000021403907"},{"@type":"NRID","@value":"9000253213545"},{"@type":"NRID","@value":"9000256474700"},{"@type":"NRID","@value":"9000241868791"},{"@type":"NRID","@value":"9000363365999"},{"@type":"NRID","@value":"9000006826192"},{"@type":"NRID","@v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Toshitaka"},{"@language":"ja","@value":"鍋島 俊隆"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine"},{"@language":"ja","@value":"名古屋大学大学院医学研究科医療薬学·医学部附属病院薬剤部"}]},{"@id":"https://cir.nii.ac.jp/crid/1420291769016422912","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"20449101"},{"@type":"NRID","@value":"1000020449101"},{"@type":"NRID","@value":"9000002745058"},{"@type":"NRID","@value":"9000021642908"},{"@type":"NRID","@value":"9000254711955"},{"@type":"NRID","@value":"9000383202563"},{"@type":"NRID","@value":"9000253264391"},{"@type":"NRID","@value":"9000272991043"},{"@type":"NRID","@value":"9000380967296"},{"@type":"NRID","@value":"9000021534882"},{"@type":"NRID","@value":"9000396096103"},{"@type":"NRID","@value":"9000253265074"},{"@type":"NRID","@value":"9000253083947"},{"@type":"NRID","@value":"9000275823065"},{"@type":"NRID","@value":"9000021552928"},{"@type":"NRID","@value":"9000383202566"},{"@type":"NRID","@value":"9000253084839"},{"@type":"NRID","@value":"9000254713383"},{"@type":"NRID","@value":"9000003130947"},{"@type":"NRID","@value":"9000282390594"},{"@type":"NRID","@value":"9000383202596"},{"@type":"NRID","@value":"9000253264395"},{"@type":"NRID","@value":"9000004947442"},{"@type":"NRID","@value":"9000383202593"},{"@type":"NRID","@value":"9000020901760"},{"@type":"NRID","@value":"9000257894017"},{"@type":"NRID","@value":"9000383202577"},{"@type":"NRID","@value":"9000242266113"},{"@type":"NRID","@value":"9000283796469"},{"@type":"NRID","@value":"9000345378850"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/y_miya1"}],"foaf:name":[{"@language":"en","@value":"MIYAMOTO Yoshiaki"},{"@language":"ja","@value":"宮本 嘉明"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Department of Molecular Genetics, National Institute for Longevity Sciences"},{"@language":"ja","@value":"国立療養所中部病院·長寿医療研究センター分子遺伝学研究部"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00155691"},{"@type":"EISSN","@value":"13478397"},{"@type":"NDL_BIB_ID","@value":"000000018989"},{"@type":"ISSN","@value":"00155691"},{"@type":"LISSN","@value":"00155691"},{"@type":"NCID","@value":"AN00198335"}],"prism:publicationName":[{"@language":"en","@value":"Folia Pharmacologica Japonica"},{"@language":"ja","@value":"日本薬理学雑誌"},{"@language":"en","@value":"Folia Pharmacol. Jpn."},{"@language":"ja","@value":"日薬理誌"},{"@language":"en","@value":"Folia Pharmacologica Japonica"},{"@language":"ja","@value":"日本薬理学雑誌"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Pharmacological Society"},{"@language":"ja","@value":"公益社団法人 日本薬理学会"}],"prism:publicationDate":"2002","prism:volume":"119","prism:number":"6","prism:startingPage":"327","prism:endingPage":"335"},"reviewed":"false","url":[{"@id":"http://id.ndl.go.jp/bib/6239638"},{"@id":"https://ndlsearch.ndl.go.jp/books/R000000004-I6239638"},{"@id":"https://search.jamas.or.jp/link/ui/2002236916"}],"availableAt":"2002","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=NMDA%20receptor","dc:title":"NMDA receptor"},{"@id":"https://cir.nii.ac.jp/all?q=GluR1%20subunit","dc:title":"GluR1 subunit"},{"@id":"https://cir.nii.ac.jp/all?q=dopaminergic%20neuronal%20system","dc:title":"dopaminergic neuronal system"},{"@id":"https://cir.nii.ac.jp/all?q=hyperlocomotion","dc:title":"hyperlocomotion"},{"@id":"https://cir.nii.ac.jp/all?q=learning%20and%20memory","dc:title":"learning and memory"},{"@id":"https://cir.nii.ac.jp/all?q=NMDA%E5%8F%97%E5%AE%B9%E4%BD%93","dc:title":"NMDA受容体"},{"@id":"https://cir.nii.ac.jp/all?q=GluR1%E3%82%B5%E3%83%96%E3%83%A6%E3%83%8B%E3%83%83%E3%83%88","dc:title":"GluR1サブユニット"},{"@id":"https://cir.nii.ac.jp/all?q=%E3%83%89%E3%83%91%E3%83%9F%E3%83%B3%E4%BD%9C%E5%8B%95%E6%80%A7%E7%A5%9E%E7%B5%8C","dc:title":"ドパミン作動性神経"},{"@id":"https://cir.nii.ac.jp/all?q=%E9%81%8B%E5%8B%95%E9%81%8E%E5%A4%9A","dc:title":"運動過多"},{"@id":"https://cir.nii.ac.jp/all?q=%E8%A8%98%E6%86%B6%C2%B7%E5%AD%A6%E7%BF%92","dc:title":"記憶·学習"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360011145748097280","@type":"Article","relationType":["references","cites"],"jpcoar:relatedTitle":[{"@value":"NMDA-receptor-dependent synaptic plasticity: multiple forms and 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