2001 Fiscal Year Annual Research Report

ナメクジの嗅覚学習における記憶形成と読み出し過程の解明

Research Project

Project/Area Number	12307053
Research Institution	The University of Tokyo
Principal Investigator	桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)
Co-Investigator(Kenkyū-buntansha)	木村哲也理化学研究所, 脳科学総合研究センター, 研究員渡辺恵東京大学, 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, 助教授 (10204752) 松尾亮太東京大学, 大学院・薬学系研究科, 助手 (40334338)
Keywords	神経修飾物質 / 連合学習 / 長期記憶 / ナメクジ / タンパク合成
Research Abstract	これまでにナメクジのin vitro標本で嗅覚学習が可能なことを示したが,本年度は嗅覚学習に伴う嗅覚中枢(前脳)での可塑性を明らかにすることを目的として,前脳の神経活動を修飾する物質の探索を行った.前脳神経活動の指標となる局所場電位振動を記録し,神経修飾物質として知られているモノアミンやセカンドメッセンジャーを前脳に投与したときの変化を測定した.その結果,セロトニンとドーパミンによって局所場電位振動の振動数が増大した.細胞内IP_3濃度を増加させる働きが知られているムスカリンは,同期振動の振動数を増加させた.またcAMPの膜透過性誘導体である8-bromo-cyclic AMPを投与すると,局所場電位振動の振幅が増大した.これらの結果から神経修飾物質が前脳神経活動の多様な修飾を担っていることが示唆された. 一方ナメクジの嗅覚-味覚連合学習の条件付けにおいて、条件付けの30分前に体腔内に、タンパク合成阻害剤であるanisomycinあるいはcycloheximideを注射すると、anisomycinの場合、条件付け後二日目以降、cycloheximideの場合、条件付け後一週間目以降の記憶保持に障害が見られた。また脳への[35S]-メチオニンの取り込みを測定したところ、anisomycinは注射後10時間までの間に最大で約90%の取り込み阻害を示したのに対し、cycloheximideでは数時間の間に最大50%程度の阻害しか示さなかった。また、anisomycin投与によって脳でのタンパク合成が十分に抑えられている時間中における、ナメクジの記憶再生そのものは影響を受けなかった。これらの結果から、タンパク合成がナメクジの嗅覚-味覚連合記憶の再生には不要であるが、その長期的な維持には必要であることが明らかになった。さらに条件付け前後のタンパク合成が阻害された場合、記憶の障害が顕著になるまでの時間と、タンパク合成の程度との間に相関が見られることが明らかになった。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Tadashi Nakaya: "Expression and Function of a Novel Gene in Odor-taste Associative Learning in the Terrestrial Slug"Genes Cells. 6. 43-56 (2001)
[Publications] Yasushi Kishimoto: "Long-trace Interval Eyeblink Conditioning Is Impaired in Mutant Mice Lacking NMDA Receptor Subunit ε1"Eur. J. Neurosci. 13. 1221-1227 (2001)
[Publications] Yasushi Kishimoto: "Classical Eyeblink Conditioning in Glutamate Receptor Subunit δ2 Mutant Mice Is Impaired in Delay Paradigm But Not in Trace Paradigm"Eur. J. Neurosci. 13. 1249-1253 (2001)
[Publications] Satoshi Watanabe: "Modulation of Oscillatory Neural Activities by Cholinergic Activation of Interneurons in the Olfactory Center of a Terrestrial Slug"Brain Res.. 896. 30-35 (2001)
[Publications] Kazuyasu Shindo: "Solution Structure of Micelle-bound H5 Peptide (427-452) : A Primary Structure Corresponding to the Pore-Forming Region of the Voltage Dependent Potassium Channel"Biochim. Biophys. Acta. 1545. 153-159 (2001)
[Publications] Yasushi Satoh: "β-Amyloid peptides inhibit acetylcholine release from cholinergic presnaptic nerve endings isolated from an e1ectric ray"Neurosci. Lett.. 302. 97-100 (2001)
[Publications] Tsuyoshi Inoue: "Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk"J. Neurophysiol. 85. 2634-2638 (2001)
[Publications] Kanako Takatsuki: "Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice"Neurophamacol. 41. 618-628 (2001)
[Publications] Kanae Ando: "Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid"J. Biol. Chem. 276. 40353-40361 (2001)
[Publications] Yasushi Kishimoto: "Impaired delay but normal trace eyeblink conditioning in PLCβ4 mutant mice"Neuroreport. 12. 2919-2922 (2001)
[Publications] Yasushi Kishimoto: "Age-dependent impairment of delay and trace eyeblink conditioning in mice"Neuroreport. 12. 3349-3352 (2001)
[Publications] Yasushi Kishimoto: "Impairment of eyeblink conditioning in GluRδ2 mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli"Enr. J. Neurosci. 14. 1515-1521 (2001)
[Publications] Moritoshi Hirono: "Phospholipase Cβ4 and Protein Kinase Cα and/or Protein Kinase CβI Are Involved in the Induction of Long-Term Depression in Cerebellar Purkinje Cells"J. Biol. Chem. 276. 45236-45242 (2001)
[Publications] Satoshi Shimozono: "Identification and characterization of an output neuron from the oscillatory molluscan olfactory network"Brain Res. 921. 98-105 (2001)
[Publications] Yoshinori Muto: "Blepharismin, produced by the protozoan, Blepharisma japonicum, form ion-permeable channels in planar lipid bilayer membranes"FEBS Lett. 508. 423-426 (2001)
[Publications] Kanako Takatsuki: "Scopolamine impairs eyeblink conditioning in the cerebellar LTD-deficient mice"NeuroReport. 13. 159-162 (2002)
[Publications] Kanako Takatsuki: "Hippocampal damage disrupts eyeblink conditioning in mice lacking glutamate receptor subunit δ2"J. Biol. Phys.. (in press). (2002)
[Publications] Yasuko Inokuma: "Two Types of Network Oscillations and Their Odor Responses in the Primary Olfactory Center of a Terrestrial Mollusk"J. Neurophysiol. (in press). (2002)
[Publications] 桐野豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)

2001 Fiscal Year Annual Research Report

ナメクジの嗅覚学習における記憶形成と読み出し過程の解明

Principal Investigator

桐野 豊 東京大学, 大学院・薬学系研究科, 教授 (10012668)

Research Products

[Publications] Tadashi Nakaya: "Expression and Function of a Novel Gene in Odor-taste Associative Learning in the Terrestrial Slug"Genes Cells. 6. 43-56 (2001)

[Publications] Yasushi Kishimoto: "Long-trace Interval Eyeblink Conditioning Is Impaired in Mutant Mice Lacking NMDA Receptor Subunit ε1"Eur. J. Neurosci. 13. 1221-1227 (2001)

[Publications] Yasushi Kishimoto: "Classical Eyeblink Conditioning in Glutamate Receptor Subunit δ2 Mutant Mice Is Impaired in Delay Paradigm But Not in Trace Paradigm"Eur. J. Neurosci. 13. 1249-1253 (2001)

[Publications] Satoshi Watanabe: "Modulation of Oscillatory Neural Activities by Cholinergic Activation of Interneurons in the Olfactory Center of a Terrestrial Slug"Brain Res.. 896. 30-35 (2001)

[Publications] Kazuyasu Shindo: "Solution Structure of Micelle-bound H5 Peptide (427-452) : A Primary Structure Corresponding to the Pore-Forming Region of the Voltage Dependent Potassium Channel"Biochim. Biophys. Acta. 1545. 153-159 (2001)

[Publications] Yasushi Satoh: "β-Amyloid peptides inhibit acetylcholine release from cholinergic presnaptic nerve endings isolated from an e1ectric ray"Neurosci. Lett.. 302. 97-100 (2001)

[Publications] Tsuyoshi Inoue: "Serotonin and NO Complementarily Regulate Generation of Oscillatory Activity in the Olfactory CNS of a Terrestrial Mollusk"J. Neurophysiol. 85. 2634-2638 (2001)

[Publications] Kanako Takatsuki: "Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice"Neurophamacol. 41. 618-628 (2001)

[Publications] Kanae Ando: "Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of β-amyloid"J. Biol. Chem. 276. 40353-40361 (2001)

[Publications] Yasushi Kishimoto: "Impaired delay but normal trace eyeblink conditioning in PLCβ4 mutant mice"Neuroreport. 12. 2919-2922 (2001)

[Publications] Yasushi Kishimoto: "Age-dependent impairment of delay and trace eyeblink conditioning in mice"Neuroreport. 12. 3349-3352 (2001)

[Publications] Yasushi Kishimoto: "Impairment of eyeblink conditioning in GluRδ2 mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli"Enr. J. Neurosci. 14. 1515-1521 (2001)

[Publications] Moritoshi Hirono: "Phospholipase Cβ4 and Protein Kinase Cα and/or Protein Kinase CβI Are Involved in the Induction of Long-Term Depression in Cerebellar Purkinje Cells"J. Biol. Chem. 276. 45236-45242 (2001)

[Publications] Satoshi Shimozono: "Identification and characterization of an output neuron from the oscillatory molluscan olfactory network"Brain Res. 921. 98-105 (2001)

[Publications] Yoshinori Muto: "Blepharismin, produced by the protozoan, Blepharisma japonicum, form ion-permeable channels in planar lipid bilayer membranes"FEBS Lett. 508. 423-426 (2001)

[Publications] Kanako Takatsuki: "Scopolamine impairs eyeblink conditioning in the cerebellar LTD-deficient mice"NeuroReport. 13. 159-162 (2002)

[Publications] Kanako Takatsuki: "Hippocampal damage disrupts eyeblink conditioning in mice lacking glutamate receptor subunit δ2"J. Biol. Phys.. (in press). (2002)

[Publications] Yasuko Inokuma: "Two Types of Network Oscillations and Their Odor Responses in the Primary Olfactory Center of a Terrestrial Mollusk"J. Neurophysiol. (in press). (2002)

[Publications] 桐野 豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)

桐野豊東京大学, 大学院・薬学系研究科, 教授 (10012668)

[Publications] 桐野豊: ""働く脳と変化する脳"「新生物物理の最前線」生物物理学会編,講談社ブルーバックス,pp.197-237"講談社. 203 (2001)