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1999 Fiscal Year Final Research Report Summary

Simple nervous system approach to the mechanisms of associative learning

Research Project

Project/Area Number 10480176
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biophysics
Research InstitutionThe University of Tokyo

Principal Investigator

KIRINO Yutaka  University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (10012668)

Co-Investigator(Kenkyū-buntansha) WATANABE Satoshi  University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学系研究科, 助手 (80302610)
KAWAHARA Shigenori  University of Tokyo, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学系研究科, 助手 (10204752)
Project Period (FY) 1998 – 1999
Keywordsassociative learning / slug / olfaction / procerebrum / extracellular matrix protein / LAPS18 / differential display
Research Abstract

This work was aimed at clarifying the mechanisms of leaning and memory using physiological and molecular biological methods. First, physiological recordings were made in the procerebrum, which is the olfactory center of the slug, in isolated bran preparations after odor-taste associative conditioning Optical recording of the membrane potential revealed that a cluster of neurons in the procerebrum depolarizes selectively in response to leaned odors.
By the mRNA differential display method, we found a gene whose expression elevated specifically after odor-taste associative conditioning, and its sequence has been determined. This gene encoded 121 amino acids, and named LAPS18. To clarify its function, the expression pattern of this gene was determined. The expression of the LAPS18 protein was significantly increased 12-48 h after conditioning compared to the control group. This suggests that the LAPS18 protein is related to the late phase events of learning. Immunohistochemical analysis indicated that LAPS18 protein was present in the entire procerebrum, and localized to the neuropil layers of the procerebrum after conditioning, indicating a conditioning-specific changes in localization. By corUoca1 laser scanning microscopy, the LAPS18 protein was found to be localized to the nerve terminals, especially regions of cell contact. These results suggest that the LAPS18 protein is an extrace11ular matrix protein secreted at nerve terminals and modulate the synaptic connections. The homologue genes of LAPS18 were found in various Vertebrate species. Therefore, LAPS18 was thought to play essential roles in learning and memory.

  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Iijima, et al.: "Phyosphyrylated Form of Alzheimer's Amyloid Precursor Protein Exists in Cholinergic Nerve Termini from Electric Ray Electric Organ"Biochem. J.. 330. 29-33 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomita, et al.: "Cleavage of Alzheimer's Amyloid Precursor Protein by Secretases Occurs after O-Glycosylation of APP in Protein Secretory Pathway"J. Biol. Chem.. 273. 6277-6284 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kojima, et al.: "Development of a Fluorescent Indicator for Nitric Oxide Based on the Fluorescein Chromophore"Chem. Pharm. Bull.. 46. 373-375 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Satoh, et al.: "Lamber-Eaton Syndrome Antibodies Inhibit Acetylcholine Release and P/Q-type Ca^<2+> Channels in Electric Ray Nerve Endings"J. Physiol.. 503. 427-438 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura, et al.: "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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kimura, et al.: "Optical Recording Analysis of Olfactory Response of the PC Lobe in the Slug Brain"Learning and Memory. 4. 389-400 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, et al.: "Morphological Characterization of the Bursting and Nonbursting Neurones in the Olfactory Centre of the Terrestrial Stug Limax marginatus"J. Exp. Biol.. 201. 925-930 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, et al.: "An Autoimmune Animal Model of the Lambert-Eaton Syndrome"Ann. N.Y. Acad. Sci.. 341. 670-676 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, et al.: "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)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomita, et al.: "A Basic Amino Acid in the Cytoplasmic Domain of Alzheimer's β-Amyloid Precursor Protein (APP) Is Essential for Cleavage of APP at the α-Site"J. Biol. Chem.. 273. 19304-19310 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kojima, et al.: "Detection and Imaging of Nitric Oxide with Novel Fluorescent Indicators: Diaminofluoresceins"Anal. Chem.. 70. 2446-2453 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桐野 豊: "学習記憶研究の戦略"「シリーズ:学習・記憶の生物物理学」"放射線医学. 41. 332-335 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lee, et al.: "Phospholipid Translocation from Outer to Inner Leaflet of Synaptic Vesicle Membranes Isolated from the Electric Organ of Japanese Electric Ray Narke japonica"J. Biochem.. 124. 798-803 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue, et al.: "Selective Optical Recording of the Neural Activity in the Olfactory Center of Land Stug Using a Calcium Indicator Dye"Bioimages. 6. 59-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagawa-Inoue, et al.: "Odorant-evoked increase in cytosolic free calcium in cultured antennal neurons of blowflies"Zool. Sci.. 15. 661-666 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] Hirakura, et al.: "Membrane Perturbation by the Alzheimer Amyloid Fragment β25-33 Requires Aggregation"Biochem. Mol. Biol. Intnl.. 46. 787-794 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomita, et al.: "Interaction of a Neuron-specific Protein Containing PDZ Domains with Alzheimer's Amyloid Precursor Protein"J. Biol. Chem.. 274. 2243-2254 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, et al.: "Glutamate Induces Cl^- and K^+ Currents in the Olfactory Intermeurons of a Terrestrial Slug"J. Comp. Physiol. A. 134. 553-562 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ando, et al.: "Role of Phosphorylation of Alzheimer's Amyloid Precursor Protein during Neuronal Differentiation"J. Neurosci.. 19. 4421-4427 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡辺 恵 他: "「ナメクジの嗅覚-味覚連合学習」(シリーズ 学習・記憶の生物物理学)"放射線科学. 42. 26-34 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川原茂敬 他: "「瞬目反射条件付けと小脳・海馬」(シリーズ 学習・記憶の生物物理学)"放射線科学. 42. 252-259 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川原茂敬 他: "遺伝子変異マウスの瞬目反射条件付け"実験医学増刊. 17. 153-158 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡辺 恵 他: "ナメクジにおける嗅覚-味覚連合学習"蛋白質核酸酵素. 45. 380-386 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桐野 豊: "基礎薬学・物理化学 スタディガイド"廣川書店. 219 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] 桐野 豊: "基礎薬学・物理化学(改訂版)"廣川書店. 460 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桐野 豊: "生命薬学シリーズ・物理化学(上)"共立出版. 217 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 桐野 豊: "生命薬学シリーズ・物理化学(下)"共立出版. 250 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 渡辺 恵: ""無脊椎動物の脳の働き"「脳研究への招待」(小幡邦彦 編)"共立出版(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomita, S., Fujita, T., Kirino, Y. and Suzuki, T.: "PDZ domain-dependent suppression of NF-kB/p65-induced Aβ42 production by a neuron-specific X11-like protein."J. Biol. Chem.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue, T., Watanabe, S., Kawahara, S. and Kirino, Y.: "In vitro odor-aversion conditioning in a terrestrial mollusc."Soc. Neurosci. Abstr.. 25. 126 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ando, K., Kirino, Y. and Suzuki, T.: "Role of Phosphorylation of Alzheimerz's Amyloid Precursor Protein during Neuronal Differentiation."J. Neurosci.. 19. 4421-4427 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomita, S., Ozaki, T., Taru, H., Oguchi, S., Takeda, S., Yagi, Y., Sakiyama, S., Kirino, Y., and Suzuki, T.: "Interaction of a Neuron-specific Protein Containing PDZ Domains with Alzheimer's Amyloid Precursor Protein."J. Biol. Chem.. 274. 2243-2254 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, S., Kawahara, S. and Kirino, Y.: "Glutamate induces ClィイD1-ィエD1 and KィイD1+ィエD1 currents in the olfactory interneurons of a terrestrial slug."J. Comp. Physiol. A. 184. 553-562 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, S., Kawahara, S. and Kirino, Y.: "Morphological characterization of the bursting and nonbursting neurones in the olfactory center of the terrestrial slug Limax marginatus."J. Exp. Biol.. 201. 925-930 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue, T., Kawahara, S., Toda, S., Watanabe, S. and Kirino, Y.: "Selective optical recording of the neural activity in the olfactory center of land slug using a calcium indicator dye."Bioimages. 6(2). 59-67 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomita, S., Kirino, Y. and Suzuki, T.: "A basic amino acid in the cytoplasmic domain of Alzheimer's β-Amyloid precursor protein (APP) is essential for cleavage of APP at the γ-site."J. Biol. Chem.. 273(30). 19304-19310 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, T., Toda, S., Sekiguchi, T. and Kirino, Y.: "Behavioral modulation induced by food odor aversive conditioning, and its influence on the olfactory responses of an osci11atory brain network in the slug, Limax marginatus."Learning and Memory. 4. 365-375 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kimura, T., Toga, S., Sekiguchi, T., Kawahara, S. and Kirino, Y.: "Optical recording analysis of olfactory response of the procerebral lobe in the slug brain."Learning and Memory. 4. 389-399 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kojima, H., Nakatsubo, N., Kikuchi, K., Kawahara, S., Kirino, Y., Nagoshi, H., Hirata, Y. and Nagano, T.: "Detection and imaging of nitric oxide with novel fluorescent indicators : diaminofluoresceins."Anal. Chem.. 70. 2446-2453 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomita, S., Kirino, Y. and Suzuki, T.: "Cleavage of Alzheimer's amyloid precursor protein by secretases occurs after O-glycosylation of APP in protein secretory pathway."J. Biol. Chem.. 273. 6277-6284 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoh, Y., Hirashima, N., Tokumaru, H., Takahashi, M. P., Kang, J., Viglione, M. P., Kim, Y. I. and Kirino, Y.: "Lambert-Eaton syndrome antibodies inhibit acetylcholine release and P/Q-type CaィイD12+ィエD1 channels in electric ray nerve endings."J. Physiol.. 508. 427-438 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iijima, K., Lee, D-S., Okutsu, J., Tomita, S., Hirashima, N., Kirino, Y. and Suzuki, T.: "Phosphorylated form of Alzheimer's amyloid precursor protein exists in cholinergic nerve termini from electric ray electric organ"Biochem. J.. 330. 29-33 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lee, D.-S., Anzai, K., Hirashima, N., Hatanaka, K., Nakamura M., Yoshioka, Y. and Kirino, Y.: "Phospholipid translocation from outer to inner leaflet of synaptic vesicle membranes isolated from the electric organ of Japanese electric ray Narke japonica."J. Biochem.. 124. 798-803 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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