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生体内物質によるシナプス可塑性および記憶・学習行動の調節機構

Research Project

Project/Area Number 12053213
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

松木 則夫  東京大学, 大学院・薬学系研究科, 教授 (70126168)

Co-Investigator(Kenkyū-buntansha) 池谷 裕二  東京大学, 大学院・薬学系研究科, 助手 (10302613)
西山 信好  東京大学, 大学院・薬学系研究科, 助教授 (20201692)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥60,200,000 (Direct Cost: ¥60,200,000)
Fiscal Year 2004: ¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2003: ¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2002: ¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2001: ¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2000: ¥12,200,000 (Direct Cost: ¥12,200,000)
Keywords記憶・学習 / シナプス可塑性 / 海馬 / 扁桃体 / ヘテロシナプス / 時空間依存性調節 / BCM曲線 / 歯状回 / 時空間的調節 / 長期増強 / 容量性Caチャネル / 海馬CA3野 / 亜鉛 / NMDA型受容体 / ヘテロシナプス長期増強 / シプナス可塑性 / ドコサヘキサエン酸 / ホスホリパーゼ / 空間学習 / 脳弓海馬采 / 長期抑圧 / 迷路学習 / 神経栄養因子
Research Abstract

今年度は海馬のシナプス可塑性調節機構についていくつか新知見を得ることが出来た。記憶に情動が関与していることは示唆されていたが、その直接的な証明や機構の解明はほとんどなされていなかった。まず、麻酔下のラットの貫通線維-歯状回顆粒細胞シナプスで刺激条件を工夫して、連続したシナプス可塑性が観察されるようにした。このシナプス可塑性は扁桃体外側基底核(BLA)に弱い刺激を与えると長期増強(LTP)が抑制されて長期抑圧(LTD)が起こりやすくなり、逆にBLAを高頻度刺激するとLTDが抑制されてLTPが増大した。BCM (Bienenstock,Cooper,Monro)曲線を描いてみるとBLAの活動レベルにより、両方向性(曲線の上下)にダイナミックに変動していた。また、この調節はその時点のBLAの活動レベルだけでなく、それ以前の活動履歴にも影響された。さらにBLA刺激は嗅内野皮質を介して間接的に歯状回シナプスを調節しており、外側貫通線維と内側貫通線維間のヘテロシナプス可塑性調整であることを明らかにした。海馬を摘出すると興奮性が失われるが実際の脳内では興奮性の上昇と低下を繰り返している。そこで摘出した海馬CA3野スライス標本に人工的に興奮性変動を与えてみた。数十ヘルツのガンマ波に相当する弱い電位変動をバックグラウンドで与えると、バックグラウンドで与えた周波数の伝達のみが特異的に増強された。また、バックグラウンドの弱い変動が存在した方が、1回刺激によるシナプス伝達の確度および神経細胞間の同期率が上昇した。さらに外液にカルバコールを加えると興奮性が上昇したが、連続的ではなく5つの状態を遷移することが明らかになった。この遷移はCA3野錐体細胞間で同期していた。これらの興奮性に依存した非線形的なシナプス伝達の変化には反回性の神経回路が重要な役割を果たしていることを示した。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All 2004 2000 Other

All Journal Article (6 results) Publications (24 results)

  • [Journal Article] Environmental Control of the Survival and Differentiation of Dentate Granule Neurons.2004

    • Author(s)
      J-A Kim et al.
    • Journal Title

      Cereb.Cortex 14

      Pages: 1358-1364

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chronometric readout from a memory trace : Gamma-frequency field stimulation recruits timed recurrent activity in the rat CA3 network.2004

    • Author(s)
      S.Fujisawa et al.
    • Journal Title

      J.Physiol.(Lond) 560

      Pages: 123-131

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Amygdala stimulation modulates hippocampal synaptic plasticity.2004

    • Author(s)
      K.Nakao et al.
    • Journal Title

      Proc.Natl.Acad.Sci.(USA) 101

      Pages: 14270-14275

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Brain-Derived Neurotrophic Factor Induces Hyperexcitable Reentrant Circuits in the Dentate Gyrus.2004

    • Author(s)
      R.Koyama et al.
    • Journal Title

      J.Neurosci. 24

      Pages: 7215-7224

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BDNF Boosts Spike Fidelity in Chaotic Neural Oscillations.2004

    • Author(s)
      S.Fujisawa et al.
    • Journal Title

      Biophys.J. 86

      Pages: 1820-1828

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BDNF locally potentiates GABAergic presynaptic machineries : Target-selective circuit inhibition.2000

    • Author(s)
      S.Ohba et al.
    • Journal Title

      Cereb.Cortex 15

      Pages: 291-298

    • Related Report
      2004 Annual Research Report
  • [Publications] A.Baba et al.: "Activity-evoked capacitative Ca^<2+> entry : Implications in synaptic plasticity"J.Neurosci.. 23. 7737-7741 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Tsukamoto et al.: "Mossy fibre synaptic NMDA receptors trigger non-Hebbian long-term potentiation at entorhino-CA3 synapses in the rat"J.Physiol.(London). 546. 665-675 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] A.Baba et al.: "Different Ca^<2+> dynamics between isolated hippocampal pyramidal cells and dentate granule cells"J.Neurocytol.. 31. 41-48 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] J-A Kim et al.: "Mossy fiber pathfinding in multilayer organotypic cultures of rat hippocampal slices."Cell Mol.Neurobiol.. 23. 115-119 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Nakao et al.: "Fimbrial control of bidirectional synaptic plasticity of medial perforant path-dentate transmission"Synapse. 47. 163-168 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] K.Sato et al.: "Estrogens inhibit L-glutamate uptake activity of astrocytes via membrane estrogen receptor α"J.Neurochem.. 86. 1498-1505 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kim et al.: "Mossy Fiber Pathfinding in Multilayer Organotypic Cultures of Rat Hippocampal Slices"Neuroscience. 113. 253-256 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueno et al.: "Mossy fiber Zn^<2+> spillover modulates heterosynaptic N-methyl-D-aspartate receptor activity in hippocampal CA3 circuits"J.Cell Biol.. 158. 215-220 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koyama et al.: "Group II metabotropic glutamate receptor activation is required for normal hippocampal mossy fibre development in the rat"J.Physiol.(Lond.). 539. 157-162 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikegaya et al.: "Rapid regrowth of hippocampal mossy fibres and preceding maturation of NMDA receptor-mediated neurotransmission"Eur.J.Neurosci.. 15. 1859-1862 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada et al.: "Brain-derived neurotrophic factor promotes the maturation of GABAergic mechanisms in cultured hippocampal neurons"J.Neuroscience. 22. 7580-7585 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukamoto et al.: "Mossy fibre synaptic NMDA receptors trigger non-Hebbian long-term potentiation at entorhino-CA3 synapses in the rat"J.Physiol.(Lond.). 546. 665-675 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki, K., Y.Ikegaya, S.Matsuura, Y.Kanai, H.Endou, N.Matsuki: "Transient Upregulation of the Glial Glutamate Transporter GLAST in Response to Fibroblast Growth Factor, Insulin-like Growth Factor and Epidermal Growth Factor in Cultured Astrocytes"J. Cell Sci.. 114. 3717-3725 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikegaya, Y., J-A Kim, M.Baba, T.Iwatsubo, N.Nishiyama, N.Matsuki: "Rapid and reversible changes in dendrite morphology and synaptic efficacy following NMDA receptor activation : Implication for a cellular defense against excitotoxicity"J. Cell Sci.. 114. 4083-4089 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakao, K., Y.Ikegaya, M.Yarnada, N.Nishiyarna, N.Matsuki: "Spatial performance correlates with long-term potentiation of the dentate gyrus but not of the CA 1 region in rats with fimbria-fornix lesions"Neurosci. Lett.. 307. 159-162 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita, S., Y.Ikegaya, M.Nishikawa, N.Nishiyarna, N.Matsuki: "Docosahexaenoic acid improves long-term potentiation attenuated by phopholipase A_2 inhibitor in rat hippocampal slices"Brit. J. Pharmacol. 132. 1417-1422 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuura, S., Y.Ikegaya, M.K.Yamada, N.Nishiyama, N.Matsuki: "Endothelin downregulates the glutamate transporter GLAST in cAMP-differentiated astrocytes in vitro"Glia. 37. 178-182 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujita, S., Y.Ikegaya, N.Nishiyarna, N.Matsuki: "Ca^<2+>-independent phospholipase A_2 inhibitor impairs spatial memory of mice"Jpn. J. Pharmacol. 83. 277-278 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Nakagami: "Laminin degradation by plasmin regulates long-term potentiation."J.Neurosci.. 20. 2003-2010 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] N.Itokazu: "Bidirectional actions of docosahexaenoic acid on hippocampal neurotransmission in vivo."Brain Res.. 862. 211-216 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Ikegaya: "Distance of target search of isolated rat hippocampal neuron is about 150 μm."Neuroscience. 97. 215-217 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Fujita: "Ca^<2+>- independent phospholipase A_2 inhibitor impairs spatial memory of mice."Jpn.J.Pharmacol.. 83. 277-278 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Sato: "Extracellular ATP reduces optically monitored electrical signals in hippocampal slices through metabolism to adenosine."Eur.J.Pharmacol.. 399. 123-129 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Ikegaya: "L-type Ca^<2+> channel blocker inhibits mossy fiber sprouting and cognitive deficits following pilocarpine seizures in immature mice."Neuroscience. 98. 647-659 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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