{"created":"2023-07-27T06:58:43.130443+00:00","id":57668,"links":{},"metadata":{"_buckets":{"deposit":"08ada949-42e3-4810-9af4-5f1aac88a450"},"_deposit":{"created_by":18,"id":"57668","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"57668"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00057668","sets":["2812:2813:2834"]},"author_link":["95632","21103"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2001-10-22","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"1998 – 1999","bibliographic_titles":[{"bibliographic_title":"平成11(1999)年度 科学研究費補助金 基盤研究(B) 研究成果報告書概要"},{"bibliographic_title":"1999 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"平成10年度の研究により、発達期小脳における過剰な登上線維シナプス除去には小脳内のNMDA受容体を介する神経活動が必要であることを明らかにした。本年度はどの時期にどのシナプスでNMDA受容体が働くことが必要であるかを検討した。NMDA受容体の拮抗剤のMK-801を発達期マウスに1日1回(0.25μg/g)腹腔に投与してNMDA受容体をブロックした。MK-801の投与時期と投与期間をいろいろに変えてマウスを成長させ、生後24日から36日の間に、登上線維の支配様式を電気生理学的に解析した。小脳スライスを作製し、プルキンエ細胞からwhole-cell patch-clamp記録を行い、登上線維を電気刺激して興奮性シナプス後電流(EPSC)を誘発した。EPSCのステップの数から、プルキンエ細胞を支配する登上線維の本数を推定した。その結果、生後15日と16日の2日間、MK-801を投与するだけで登上線維多重支配の残存が起こることが明らかになった。また、この時期にはプルキンエ細胞のEPSCにはNMDA受容体成分は存在せず、苔状線維と顆粒細胞の間のEPSCには大きなNMDA受容体成分が認められた。これらの結果から、生後15日と16日の2日間に苔状線維―顆粒細胞間シナプスのNMDA受容体を介する神経活動が顆粒細胞の軸索である平衡線維を通じてプルキンエ細胞に伝えられ、平行線維とプルキンエ細胞間のシナプスにおいて代謝型グルタミン酸受容体1型(mGluR1)からγ型プロテインキナーゼC(PKCγ)にいたるカスケードを活性化することが登上線維シナプス除去に必要であることが示唆された。また、上記のカスケードのほかに、hterleukin-6やInsulin-like growth factorなどが関与するという予備的な結果を得たが、これらはmGluR1カスケードとは別の機構を介するものと考えられた。","subitem_description_type":"Abstract"},{"subitem_description":"The climbing fiber to Purkinje cell synapse in the cerebellum has been a good model to study cellular and molecular mechanisms of synapse elimination by which redundant connections formed earlier during development are refined. In early postnatal days of rodents' life, most Purkinje cells are innervated by multiple climbing fibers. Then, elimination of supernumerary climbing fibers occurs until the one-to-one relations between climbing fibers and Purkinje cells are attained at approximately postnatal day 21 (P21). This relationship is maintained throughout life. This process has been shown to depend on neural activity involving NMDA receptors (Rabacchi et al., 1991). In the present study, we found that continuous and local application of tetrodotoxin or an NMDA receptor antagonist, MK-801 to developing mouse cerebella resulted in persistent multiple climbing fiber-innervation in about 40% of Purkinje cells. We also demonstrated that blockade of NMDA receptor-mediated neural activity in the cerebellum during P15-P16, but not before nor after this period, caused persistent multiple climbing fiber innervation. as well as motor discoordination. The NMDA receptor blockade did not cause apparent change in cerebellar morphology and basic synaptic properties. Our results suggest that the NMDA receptor-dependent climbing fiber synapse elimination is achieved during this critical period, and its disruption leads to persistent impairment of cerebellar function. By using gene deletion technique in mice, we have demonstrated previously that the signal transduction involving metabotropic glutamate receptor subtype l (mGluR1), the α subunit Gq (Gαq), phospholipase Cβ4 (PLCβ4) and protein kinase Cγ(PKCγ) is required for climbing fiber synapse elimination during the third postnatal week that coincide with the critical period revealed in the present study. We assume that neural activity along the mossy fiber-granule cell-parallel fiber pathway activates mGluR1 and the following cascade in Purkinje cells that is required for elimination of supernumerary climbing fibers.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:10480230, 研究期間(年度):1998 – 1999","subitem_description_type":"Other"},{"subitem_description":"出典：「発達期小脳における、神経活動に依存した過剰な興奮性シナプス除去の分子機構の解明」研究成果報告書　課題番号10480230\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10480230/104802301999kenkyu_seika_hokoku_gaiyo/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学医学部","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00063938","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=40185963"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=40185963","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10480230/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10480230/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10480230/104802301999kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-10480230/104802301999kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-09-16"}],"displaytype":"detail","filename":"ME-PR-KANO-M-kaken 2001-3p.pdf","filesize":[{"value":"134.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KANO-M-kaken 2001-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/57668/files/ME-PR-KANO-M-kaken 2001-3p.pdf"},"version_id":"a456177f-c8a2-4842-93ae-973238aebb4b"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"発達期小脳における、神経活動に依存した過剰な興奮性シナプス除去の分子機構の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"発達期小脳における、神経活動に依存した過剰な興奮性シナプス除去の分子機構の解明"},{"subitem_title":"Molecular Mechanisms for Activity-dependent Elimination of Supernumerary Excitatory Synapses in Developing Cerebellum","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2834"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-09-16"},"publish_date":"2021-09-16","publish_status":"0","recid":"57668","relation_version_is_last":true,"title":["発達期小脳における、神経活動に依存した過剰な興奮性シナプス除去の分子機構の解明"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:55:39.406620+00:00"}