1998 年度実績報告書

連合学習機構解明へのSimple Nervous System Approach

研究課題

研究課題/領域番号	10480176
研究機関	東京大学
研究代表者	桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)
研究分担者	渡辺恵東京大学, 大学院・薬学系研究科, 助手 (80302610) 川原茂敬東京大学, 大学院・薬学系研究科, 助手 (10204752)
キーワード	嗅覚-味覚連合学習 / コウラナメクジ / 単離脳 / イメージング / 膜電位感受性色素 / cDNA / 5'-RACE法
研究概要	本研究は連合学習における普遍的な神経メカニズムを,単純な神経系を持つ軟体動物であるナメクジの嗅覚-味覚連合学習系を用いて,生理学的手法と分子生物学的手法により解明することを目指している.はじめに学習依存的な神経活動を明らかにする目的で,学習を担う脳部位である前脳の光学測定を行った.誘引性の匂い(条件刺激)と忌避性の苦味物質(無条件刺激)を用いて条件付けを行ったナメクジから取り出した脳を膜電位感受性色素(Molecular Probes,di-4-ANEPPS)で染色し,2次元光量差分計測装置(富士写真フィルム,HR Deltaron1700)を用いて,匂い刺激に対する応答を記録した.その結果,前脳の中のバンド状の領域において,条件付けした匂いに対して特異的に脱分極応答が生じることが明らかになった.このことから,前脳には学習依存的な神経可塑性が存在することが示唆された. 一方これまでの研究で,前脳に学習依存的に発現量が変化する遺伝子が数個存在することを明らかにしてきた.これらの遺伝子は生理学的測定から示唆される学習依存的な神経可塑性に重要な役割を果たしていることが予想される.そこで本年度は特に発現量変化の大きい1つの遺伝子について,機能の解明を目指して解析を進めた.はじめにcDNAの全長を5'-RACE法を用いて決定した.得られたcDNA全長580bpで,121個のアミノ酸をコードしていた.この遺伝子のホモログ遺伝子をGenome ProjectおよびEST Projectのデータベースから探索したところ,線虫,マウスおよびヒトでホモログ遺伝子が存在していた.この遺伝子が種を超えて広く存在していることは,細胞内情報伝達などの普遍的で重要な機能を示唆している.

研究成果

(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Ko-ichi Iijima: "Phosphorylated Form of Alzheimer's Amyloid Precursor Protein Exists in Cholinergic Nerve T ermini from Electric Ray Electric Organ" Biochem.J.330. 29-33 (1998)
[文献書誌] Susumu Tomita: "Cleavage of Alzeheimer's Amyloid Precursor Protein by Secretases Occurs after O-glycosyla-tion of APP in Protein Secretory Pathway" J.Biol.Chem.273. 6277-6284 (1998)
[文献書誌] Hirotasu Kojima: "Development of a Fluorescent Indicator for Nitric Oxide Based on the Fluorescein Chromophore" Chem.Pharm.bull.46. 373-375 (1998)
[文献書誌] Yasushi Satoh: "Lambert-Eaton Syndrome Antibodies Inhibit Acetylcholine Release and P/Q-type Ca^<2+> Channels in Electric Ray Nerve Endings" J.Physiol.508. 427-438 (1998)
[文献書誌] Tetsuya Kimura: "Behavioral Modulation Induced by Food-Odor Aversive Conditioning, and Its Influence on the Olfactory Responses of an Oscillatory Brain Network in the Slug.Limax marginatus" Learning and Memory. 4. 365-375 (1998)
[文献書誌] Tetsuya Kimura: "Optical Recording Analysis of Olfactory Response of the PC Lobe in the Slug Brain" Learning and Memory. 4. 389-400 (1998)
[文献書誌] Satoshi Watanabe: "Morphological Characterization of the Bursting and Nonbursting Neurons in the Olfactory Center of the Terrestrial Slug Limax marginatus" J.Exp.Biol.201. 925-930 (1998)
[文献書誌] Yong I.Kim: "An Autoimmune Animal Model of the Larnbert-Eaton Syndrom" Ann.N.Y.Acad.Sci. 841. 670-676 (1998)
[文献書誌] Shigeo Watanabe: "Differential Roles of Two Types of Voltage-gated Ca^<2+> Channels in the Dendrites of Rat Cerebellar Purkinje Neurons" Brain Res.791. 43-55 (1998)
[文献書誌] Susumu Tomita: "A Basic Amino Acid in the Cytopolasmic Domain of Altzheimer's β-Amyloid Precursor Protein(APP)Is Essential for Cleavage of APP at the a-site" J.Biol.Chem.273. 19304-19310 (1998)
[文献書誌] Hirotatsu Kojima: "Detection and Imaging of Nitric Oxide with Novel Fluorescent Indicators:Diaminofluoresceins" Anal.Chem.70. 2446-2453 (1998)
[文献書誌] 桐野豊: "学習記憶研究の戦略" 放射線医学. 38. 174-177 (1998)
[文献書誌] Dong-Seok Lee: "Phospholipid Translocation from Outer to Inner Leaflet of Synaptic Vesicle membranes Isolated from the Electric Organ of Japanese Eletric Ray Narke japonica" J.Biochem.124. 798-803 (1998)
[文献書誌] Tsuyoshi Inoue: "Selective Optical Recording of the Neural Activity in the Olfactory Center of Land Slug Using a Calcium Indicator Dye" Bioimages. 6. 59-67 (1998)
[文献書誌] Azusa Nakagawa-Inoue: "Odorant-evoked Increase in Cytosolic Free Calcium in Cultured Anntenal Neurons of Blowfies" Zool.Sci.15. 661-666 (1998)
[文献書誌] Yutaka Hirakura: "Membrane Perturbation by the Alzheimer Amyloid Fragment β25-35 Requires Aggregation" Biochem.Mol.Biol.Intnl.46. 787-794 (1998)
[文献書誌] Susumu Tomita: "Interaction of a Neuron-specific Protein Containing PDZ Domains with Alzheimer's Amyloid Precursor Protein" J.Biol.Chem.274. 2243-2254 (1999)
[文献書誌] Satoshi Watanabe: "Glutamate Induces Cl^- and K^+ Currents in the Olfacotry Interneurons of a Terrestrial Slug" J.Comp.Physiol.A. (in press). (1999)
[文献書誌] Kanae Ando: "Role of Phsphorylation of Alzheimer's Amyloid Precursor Protein during Neuronal Differentiation" J.Neurosci.(in press). (1999)
[文献書誌] 桐野豊: "基礎薬学物理化学(改訂版)" 廣川書店(in press), (1999)

1998 年度 実績報告書

連合学習機構解明へのSimple Nervous System Approach

研究代表者

桐野 豊 東京大学, 大学院・薬学系研究科, 教授 (10012668)

研究成果

[文献書誌] Ko-ichi Iijima: "Phosphorylated Form of Alzheimer's Amyloid Precursor Protein Exists in Cholinergic Nerve T ermini from Electric Ray Electric Organ" Biochem.J.330. 29-33 (1998)

[文献書誌] Susumu Tomita: "Cleavage of Alzeheimer's Amyloid Precursor Protein by Secretases Occurs after O-glycosyla-tion of APP in Protein Secretory Pathway" J.Biol.Chem.273. 6277-6284 (1998)

[文献書誌] Hirotasu Kojima: "Development of a Fluorescent Indicator for Nitric Oxide Based on the Fluorescein Chromophore" Chem.Pharm.bull.46. 373-375 (1998)

[文献書誌] Yasushi Satoh: "Lambert-Eaton Syndrome Antibodies Inhibit Acetylcholine Release and P/Q-type Ca^<2+> Channels in Electric Ray Nerve Endings" J.Physiol.508. 427-438 (1998)

[文献書誌] Tetsuya Kimura: "Behavioral Modulation Induced by Food-Odor Aversive Conditioning, and Its Influence on the Olfactory Responses of an Oscillatory Brain Network in the Slug.Limax marginatus" Learning and Memory. 4. 365-375 (1998)

[文献書誌] Tetsuya Kimura: "Optical Recording Analysis of Olfactory Response of the PC Lobe in the Slug Brain" Learning and Memory. 4. 389-400 (1998)

[文献書誌] Satoshi Watanabe: "Morphological Characterization of the Bursting and Nonbursting Neurons in the Olfactory Center of the Terrestrial Slug Limax marginatus" J.Exp.Biol.201. 925-930 (1998)

[文献書誌] Yong I.Kim: "An Autoimmune Animal Model of the Larnbert-Eaton Syndrom" Ann.N.Y.Acad.Sci. 841. 670-676 (1998)

[文献書誌] Shigeo Watanabe: "Differential Roles of Two Types of Voltage-gated Ca^<2+> Channels in the Dendrites of Rat Cerebellar Purkinje Neurons" Brain Res.791. 43-55 (1998)

[文献書誌] Susumu Tomita: "A Basic Amino Acid in the Cytopolasmic Domain of Altzheimer's β-Amyloid Precursor Protein(APP)Is Essential for Cleavage of APP at the a-site" J.Biol.Chem.273. 19304-19310 (1998)

[文献書誌] Hirotatsu Kojima: "Detection and Imaging of Nitric Oxide with Novel Fluorescent Indicators:Diaminofluoresceins" Anal.Chem.70. 2446-2453 (1998)

[文献書誌] 桐野 豊: "学習記憶研究の戦略" 放射線医学. 38. 174-177 (1998)

[文献書誌] Dong-Seok Lee: "Phospholipid Translocation from Outer to Inner Leaflet of Synaptic Vesicle membranes Isolated from the Electric Organ of Japanese Eletric Ray Narke japonica" J.Biochem.124. 798-803 (1998)

[文献書誌] Tsuyoshi Inoue: "Selective Optical Recording of the Neural Activity in the Olfactory Center of Land Slug Using a Calcium Indicator Dye" Bioimages. 6. 59-67 (1998)

[文献書誌] Azusa Nakagawa-Inoue: "Odorant-evoked Increase in Cytosolic Free Calcium in Cultured Anntenal Neurons of Blowfies" Zool.Sci.15. 661-666 (1998)

[文献書誌] Yutaka Hirakura: "Membrane Perturbation by the Alzheimer Amyloid Fragment β25-35 Requires Aggregation" Biochem.Mol.Biol.Intnl.46. 787-794 (1998)

[文献書誌] Susumu Tomita: "Interaction of a Neuron-specific Protein Containing PDZ Domains with Alzheimer's Amyloid Precursor Protein" J.Biol.Chem.274. 2243-2254 (1999)

[文献書誌] Satoshi Watanabe: "Glutamate Induces Cl^- and K^+ Currents in the Olfacotry Interneurons of a Terrestrial Slug" J.Comp.Physiol.A. (in press). (1999)

[文献書誌] Kanae Ando: "Role of Phsphorylation of Alzheimer's Amyloid Precursor Protein during Neuronal Differentiation" J.Neurosci.(in press). (1999)

[文献書誌] 桐野 豊: "基礎薬学 物理化学(改訂版)" 廣川書店(in press), (1999)

1998 年度実績報告書

桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)

[文献書誌] 桐野豊: "学習記憶研究の戦略" 放射線医学. 38. 174-177 (1998)

[文献書誌] 桐野豊: "基礎薬学物理化学(改訂版)" 廣川書店(in press), (1999)