1997 Fiscal Year Annual Research Report

生理学的・分子生物学的アプローチの統合による大脳運動関連領野の機能解析

Research Project

Project/Area Number	08044236
Research Institution	Tohoku University
Principal Investigator	丹治順東北大学, 医学部, 教授 (10001885)
Co-Investigator(Kenkyū-buntansha)	GRAYBIEL Ann マサチューセッツ工科大学, 工学部, 教授渡部雅彦北海道大学, 医学部, 助教授 (70210945) 嶋啓節東北大学, 医学部, 助手 (60124583) 虫明元東北大学, 医学部, 助教授 (80219849) 蔵田潔弘前大学, 医学部, 教授 (30170070)
Keywords	霊長類 / 脳機能 / 生理学的解析 / 分子生物学的解析 / 免疫組織化学 / 最初期遺伝子 / NMDA受容体サブユニット
Research Abstract	大脳運動関連領野の機能を解析するために,生理学的手法と分子生物学的手法を統合した研究を進め,成果を得ることができた.特に霊長類を対象とした分子生物学的アプローチを,生理機能との関連において実験研究に導入したことが本研究の特色である.そのために国内・国外の研究者が協力し,緊密な研究連絡のもとに研究を進め,共同研究を行うことによって以下の項目について研究が進展した. 大脳基底核と大脳皮質の機能的な連絡すなわち大脳皮質-基底核連関の構造と機能について新しい知見が得られた.線状体の出力は直接系と関節系に分けられる.この2系の機能的意義を知るために,まず大脳運動野を生理学的にマッピングし,次に微小電極によって2時間連続的に微小刺激を加えた.刺激直直ちに脳を灌流固定し,最初期遺伝子であるc-fosならびにjun Bの発現を免疫組織化学の手法で検出した.同時にEnkephalin細胞を免疫組織化学的に検出した.その結果,一次運動野刺激後のjun B発現細胞の多くはEnkephalin含有細胞であることが判明した.この次は一次運動野から線状体への入力が,いわゆる間接系に多く分布することを示している.次に補足運動野を生理学的にマッピングし,微小刺激後のIEG発現の検討では,IEG陽性細胞とEnkephalin陽性細胞の分布は重複が少ないことが判明した.このことは,補足運動野-線状体系がいわゆる直接系に強く入力することを示しており,これらの知見は大脳運動野-基底核連関の機能構築の理解に関し,極めて重要な知見を提供したと言える. in situハイブリダイゼーション法によって,霊長類の大脳におけるNMDA受容体サブユニット発現解析を行った.生理学的に部位同定をまず行い,次に新鮮脳から凍結切片を作成し35S標識のオリゴヌクレオチドプローブを用いて解析を行った.受容体のうちGluE ε1,ε2,ζの3種のサブユニットはそれぞれ大脳運動野,運動前野前頭前野に於て異なる分布をすることが判明した.特に皮質層構造における分布のちがいが顕著であった.次にNMDA受容体のサブユニット抗体が得られたので,蛋白レベルでの分布も検索中である.

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Mushiake H, Tanatsugu Y, Tanji J.: "Neuronal activity in the ventral part of premotor cortex during target-reach movement is modulated by direction of gaze." Journal of Neurophysiology. 78. 567-571 (1997)
[Publications] Inase M, LiB-M, Tanji T.: "Dopaminergic modulation of neuronal activity in the monkey putam en through D1 and D2 receptors during a delayed go/nago task" Experimental Brain Research. 117. 207-218 (1997)
[Publications] Nakagawa S.Watanabe M.Isobe T.Kondo H.& Inoue Y.: "Cytological compartmentalization in the staggerer cerebellum as revealed by calbindin immunohistochemistry for Purkinje cells." J.Comp.Neurol.(in press).
[Publications] Manya H.Aoki J.Watanabe M.Adachi T.Asou H.Inoue Y.Araki H.& Inoue K.: "Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain." J.Biol.Chem. (in press).
[Publications] Watanabe M.Nakamura M.Sato K.Kano M.Simon MI&Y.Inoue: "Distinct expressions and distributions of phospholipase Cβ1-4 mRNAs in developing and adult mouse brains." Eur.J.Neurosci.(in press).
[Publications] Watase.Hashimoto.Kano.YamadaK.WatanabeM.Inoue.Okuyama.Sakagawa.Ogawa.Kawashima.Hori.Takimoto.Wada & Tanaka.: "Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice." Eur.J.Neurosci.10. 976-988 (1998)
[Publications] Offermanns S.Hashimoto K.Watanabe M.Sun W.Kurihara H.Thompson R.F.Inoue Y.Kano M.Simon M.T.: "Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells of mice lacking Gαa." Proc.Natl.Acad.Sci.USA. 94. 14089-14094 (1997)
[Publications] Shibata T.Yamada K.Watanabe M.Ikenaka K.Wada K.Tanaka K.Inouw Y.: "Glutamate Transporter GLAST is Expressed in the Radial Glia-Astrocyte Lineage of Developing Mouse Spinal Cord." J.Neurosci.17. 9212-9219 (1997)
[Publications] Itoh M.Watanabe Y.Watanabe M.Tanaka K.Wada K.& Takashima S.: "Expression of a glutamate transporter subtype EAAT4 in the developing human cerebellum." Brain Res.767. 265-271 (1997)
[Publications] Tanaka J.Jchikawa R.Watanabe M.Tanaka K.& Inoue Y.: "EAAT4 at excitatory Purkinje cell synaExtra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses.8:2.pses." Neuroreport. 8. 2461-2464 (1997)
[Publications] Kohyama-Koganeya A.Watanabe M.& Hotta G.: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in rat retina." FEBS Lett.409. 258-264 (1997)
[Publications] Nakagawa S.Watanabe M.& Inoue Y.: "Prominent expression of nuclear hormone receptor ROR α in Purkinje cells from early development." N seurosci.Res.28. 177-184 (1997)
[Publications] Ito L.Futai K.Katagiri H.Watanabe M.Sakimura K.Mishina M.Sugiyama H.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J.Physiol.500. 401-408 (1997)
[Publications] Berretta S, Parthasarathy HB, & Graybuel AM.: "Local release of GABAergic inhibition in the motor cortex induces immediate early gene expression in indirect path way neurons of the striatum" J.Neurosci.17. 4752-4763 (1997)
[Publications] Parthasarathy HB & Graybiel AM: "Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrelmonkey." J.Neurosci. 17. 2477-2491 (1997)
[Publications] Holt D, Graybiel AM & Saper CB.: "Neurochemical architecture of the human striatum." J.Comp.Neurol.384. 1-25 (1997)
[Publications] XuM, Koezow TE, Saniago GT, Moratalla R, Cooper DC, HuX-T, WhmeNM, Graybiel AM, WhieFL TonegawaS.: "Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors." Neuron. 19. 837-848 (1997)
[Publications] Graybiel AM.: "The basal ganglia and cognitive pattern generators." Schizophrenia Bulletin. 23. 459-469 (1997)
[Publications] Tanji J, Shima K, Mushiake H.: "Brain and Mind" M.Ito, 223-232 (1997)
[Publications] 丹治順: "医学書院" 岩本誠,寺本明,清水輝夫, 134- (1997)
[Publications] Liu F-C & Graybiel AM: "Catecholamines(AdVances in Pharmacology,Vol42)" David S.Goldstein,Graeme Eisenhofer & Richard McCarty., 682-686 (1997)

1997 Fiscal Year Annual Research Report

生理学的・分子生物学的アプローチの統合による大脳運動関連領野の機能解析

Principal Investigator

丹治 順 東北大学, 医学部, 教授 (10001885)

Research Products

[Publications] Mushiake H, Tanatsugu Y, Tanji J.: "Neuronal activity in the ventral part of premotor cortex during target-reach movement is modulated by direction of gaze." Journal of Neurophysiology. 78. 567-571 (1997)

[Publications] Inase M, LiB-M, Tanji T.: "Dopaminergic modulation of neuronal activity in the monkey putam en through D1 and D2 receptors during a delayed go/nago task" Experimental Brain Research. 117. 207-218 (1997)

[Publications] Nakagawa S.Watanabe M.Isobe T.Kondo H.& Inoue Y.: "Cytological compartmentalization in the staggerer cerebellum as revealed by calbindin immunohistochemistry for Purkinje cells." J.Comp.Neurol.(in press).

[Publications] Manya H.Aoki J.Watanabe M.Adachi T.Asou H.Inoue Y.Araki H.& Inoue K.: "Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain." J.Biol.Chem. (in press).

[Publications] Watanabe M.Nakamura M.Sato K.Kano M.Simon MI&Y.Inoue: "Distinct expressions and distributions of phospholipase Cβ1-4 mRNAs in developing and adult mouse brains." Eur.J.Neurosci.(in press).

[Publications] Watase.Hashimoto.Kano.YamadaK.WatanabeM.Inoue.Okuyama.Sakagawa.Ogawa.Kawashima.Hori.Takimoto.Wada & Tanaka.: "Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice." Eur.J.Neurosci.10. 976-988 (1998)

[Publications] Offermanns S.Hashimoto K.Watanabe M.Sun W.Kurihara H.Thompson R.F.Inoue Y.Kano M.Simon M.T.: "Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells of mice lacking Gαa." Proc.Natl.Acad.Sci.USA. 94. 14089-14094 (1997)

[Publications] Shibata T.Yamada K.Watanabe M.Ikenaka K.Wada K.Tanaka K.Inouw Y.: "Glutamate Transporter GLAST is Expressed in the Radial Glia-Astrocyte Lineage of Developing Mouse Spinal Cord." J.Neurosci.17. 9212-9219 (1997)

[Publications] Itoh M.Watanabe Y.Watanabe M.Tanaka K.Wada K.& Takashima S.: "Expression of a glutamate transporter subtype EAAT4 in the developing human cerebellum." Brain Res.767. 265-271 (1997)

[Publications] Tanaka J.Jchikawa R.Watanabe M.Tanaka K.& Inoue Y.: "EAAT4 at excitatory Purkinje cell synaExtra-junctional localization of glutamate transporter EAAT4 at excitatory Purkinje cell synapses.8:2.pses." Neuroreport. 8. 2461-2464 (1997)

[Publications] Kohyama-Koganeya A.Watanabe M.& Hotta G.: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in rat retina." FEBS Lett.409. 258-264 (1997)

[Publications] Nakagawa S.Watanabe M.& Inoue Y.: "Prominent expression of nuclear hormone receptor ROR α in Purkinje cells from early development." N seurosci.Res.28. 177-184 (1997)

[Publications] Ito L.Futai K.Katagiri H.Watanabe M.Sakimura K.Mishina M.Sugiyama H.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J.Physiol.500. 401-408 (1997)

[Publications] Berretta S, Parthasarathy HB, & Graybuel AM.: "Local release of GABAergic inhibition in the motor cortex induces immediate early gene expression in indirect path way neurons of the striatum" J.Neurosci.17. 4752-4763 (1997)

[Publications] Parthasarathy HB & Graybiel AM: "Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrelmonkey." J.Neurosci. 17. 2477-2491 (1997)

[Publications] Holt D, Graybiel AM & Saper CB.: "Neurochemical architecture of the human striatum." J.Comp.Neurol.384. 1-25 (1997)

[Publications] XuM, Koezow TE, Saniago GT, Moratalla R, Cooper DC, HuX-T, WhmeNM, Graybiel AM, WhieFL TonegawaS.: "Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors." Neuron. 19. 837-848 (1997)

[Publications] Graybiel AM.: "The basal ganglia and cognitive pattern generators." Schizophrenia Bulletin. 23. 459-469 (1997)

[Publications] Tanji J, Shima K, Mushiake H.: "Brain and Mind" M.Ito, 223-232 (1997)

[Publications] 丹治 順: "医学書院" 岩本誠,寺本明,清水輝夫, 134- (1997)

[Publications] Liu F-C & Graybiel AM: "Catecholamines(AdVances in Pharmacology,Vol42)" David S.Goldstein,Graeme Eisenhofer & Richard McCarty., 682-686 (1997)

丹治順東北大学, 医学部, 教授 (10001885)

[Publications] 丹治順: "医学書院" 岩本誠,寺本明,清水輝夫, 134- (1997)