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Mechanisms underlying action of neurotrophic factors on postsynaptic glutamate and GABA receptors

Research Project

Project/Area Number 14208094
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionOsaka University

Principal Investigator

TSUMOTO Tadaharu  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50028619)

Co-Investigator(Kenkyū-buntansha) 茜谷 行雄  大阪大学, 医学系研究科, 助手 (40222517)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥54,470,000 (Direct Cost: ¥41,900,000、Indirect Cost: ¥12,570,000)
Fiscal Year 2004: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2003: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2002: ¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000)
KeywordsNeurotrophic factor / GABA / BDNF / GFP / Dendrites / Synapse / Glutamate receptor / Neuron culture / 脳 / 培養神経細胞 / 抑制性ニューロン / 脳由来神経栄養因子 / 抑制性伝達物質 / 抑制性シナプス
Research Abstract

Previously we found that brain-derived neurotrophic factor (BDNF) is released from presynaptic sites in an activity-dependent manner and acts on postsynaptic neurons. In this study we attempted to see whether actions of BDNF are different between glutamatergic excitatory synapses and GABAergic inhibitory synapses, and further to elucidate mechanisms underlying such actions. We obtained the following results.
1.Using mixed neuron culture preparations obtained from green fluorescence protein (GFP) mice and BDNF knockout mice, we explored what actions presynaptic BDNF exerts on postsynaptic neurons. We found that presynaptic BDNF promotes dendritic development of postsynaptic GABAergic neurons.
2.Actions of exogenous BDNF on GABAergic synapses were investigated in solitary GABAergic neurons cultured on glial microisland to completely exclude possible involvement of excitatory synapses from the observed effects of BDNF. We found that BDNF increased the number of active GABAergic synapses.
3.Roles of endogenous BDNF in development of glutamatergic synapses were investigated in barrel cortex of BDNF knockout and wild type mice. We found that silent synapses, which consist only of NMDA receptors, are abnormally increased in BDNF knockout mice, and this is rescued by exogenously applied BDNF.
4.Actions of exogenous BDNF on excitatory synapses on GABAergic neurons were not studied previously. We addressed this issue by using GAD67-GFP knock-in mice, in which GABAergic neurons are easily identified. We found that BDNF acutely depressed function of excitatory synapses to GABAergic neurons.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (29 results)

All 2005 2004 2003 Other

All Journal Article (17 results) Publications (12 results)

  • [Journal Article] RNAi-induced gene silencing by local electroporation in targeting brain region.2005

    • Author(s)
      Akaneya, Y. et al.
    • Journal Title

      J.Neurophysiol. 93

      Pages: 594-602

    • Related Report
      2004 Annual Research Report
  • [Journal Article] NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling.2005

    • Author(s)
      Hori, K. et al.
    • Journal Title

      J.Neurosci. 25(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex2004

    • Author(s)
      Palizvan MR, Sohya K, Kohara K, Maruyama A, Yasuda H, Kimura F, Tsumoto T.
    • Journal Title

      Neuroscience 126

      Pages: 955-966

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices2004

    • Author(s)
      Jiang B, Kitamura A, Yasuda H, Sohya K, Maruyama A, Yanagawa Y., Obata K, Tsumoto, T.
    • Journal Title

      European Journal of Neuroscience 20

      Pages: 709-718

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex.2004

    • Author(s)
      PALZVAN MR, SOHYA K, KOHARA K, MARUYAMA A, YASUDA H, KIMURA F, TSUMOTO, T.
    • Journal Title

      Neuroscience 126

      Pages: 955-966

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices.2004

    • Author(s)
      JIANG B, KITAMURA A, YASUDA H, SOHYA K, MARUYAMA A, YANAGAWA Y., OBATA K, TSUMOTO, T.
    • Journal Title

      Europ.J.Neurosci. 20

      Pages: 709-718

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices.2004

    • Author(s)
      Jiang, B. et al.
    • Journal Title

      Europ.J.Neurosci. 20

      Pages: 709-718

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transiently higher release probability during critical period at thalamocortical synapses in the mouse barrel cortex : relevance to differential short-term plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses.2004

    • Author(s)
      Yanagisawa, T. et al.
    • Journal Title

      Europ.J Neurosci. 20

      Pages: 3006-3018

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Brain-derived neurotrophic factor increases inhibitory synapses, revealed in solitary neurons cultured from rat visual cortex.2004

    • Author(s)
      Palizvan, M.R. et al.
    • Journal Title

      Neuroscience 126

      Pages: 955-966

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibitory but not excitatory cortical neurons require presynaptic brain-derived neurotrophic factor for dendritic development, as revealed by chimera cell culture2003

    • Author(s)
      Kohara K, Kitamura A, Adachi N, Nishida M, Itami C, Nakamura S, Tsumoto, T
    • Journal Title

      Journal of Neuroscience 23

      Pages: 6123-6131

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BDNF-dependent unmasking of "silent" synapses in developing mouse barrel cortex2003

    • Author(s)
      Itami C, Kimura F, Kohno T, Matsuoka M, Ichikawa M, Tsumoto T, Nakamura, S
    • Journal Title

      Proceedings of National Academy of Sciences USA 100

      Pages: 13069-13074

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term depression is not induced by low frequency stimulation in rat visual cortex in vivo : A possible preventing role of endogenous BDNF2003

    • Author(s)
      Jiang, B., Akaneya, Y., Hata, Y., Tsumoto, T.
    • Journal Title

      Journal of Neuroscience 23

      Pages: 3761-3770

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex2003

    • Author(s)
      Salami M, Itami C, Tsumoto T, Kimura F.
    • Journal Title

      Proceedings of National Academy of Sciences USA 100

      Pages: 6174-6179

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory but not excitatory cortical neurons require presynaptic brain-derived neurotrophic factor for dendritic development, as revealed by chimera cell culture2003

    • Author(s)
      KOHARA K, KITAMURA A, ADACHI N, NISHIDA M, ITAMI C, NAKAMURA S, TSUMOTO T.
    • Journal Title

      J.Neurosci. 23

      Pages: 6123-6131

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] BDNF-dependent unmasking of "silent" synapses in developing mouse barrel cortex.2003

    • Author(s)
      ITAMI C, KIMURA F, KOHNO T, MATSUOKA M, ICHIKAWA M, TSUMOTO T, NAKAMURA S.
    • Journal Title

      Proc.Nat.Acad.Sci.USA 100

      Pages: 13069-13074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Long-term depression is not induced by low frequency stimulation in rat visual cortex in vivo : A possible preventing role of endogenous BDNF.2003

    • Author(s)
      JIANG B, AKANEYA Y, HATA Y, TSUMOTO T.
    • Journal Title

      J.Neurosci. 23

      Pages: 3761-3770

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex.2003

    • Author(s)
      SALAMI M, ITAMI C, TSUMOTO T, KIMURA F.
    • Journal Title

      Proc.Nat.Acad.Sci.USA 100

      Pages: 6174-6179

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ichisaka, S.et al.: "Activity-dependent changes in the Protein level of brain-derived neurotrophic factor but no change in other neurotrophins in the visual cortex of young and adult ferrets"Neuroscience. 117. 361-371 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akaneya, Y.et al.: "Low-frequency depression of synaptic responses recorded from rat visual cortex"Neuroscience. 117. 305-320 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Jiang, B.et al.: "Long-term depression is not induced by low frequency stimulation in rat visual cortex in vivo : A possible preventing role of endogenous BDNF"J.Neurosci.. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Salami, M. et al.: "Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex"Proc.Nat.Acad.Sci.USA. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kohara, K. et al.: "Inhibitory, but not excitatory cortical neurons require presynaptic BDNF for dendritic development, as revealed by chimera cell culture"J.Neurosci. 23. 6123-6131 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Itami, C.et al.: "BDNF-dependent unmasking of"silent"synapses in developing mouse barrel cortex"Proc.Nat.Acad.Sci.USA. 100. 13069-13074 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohshima, M.et al.: "Chronic, electrical stimulation of afferents from one eye changes ocular dominance of visual corticalneurones in kittens"J.Neurophysiol.. 88. 2147-2151 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yasuda, H.et al.: "Imaging of calcineuin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex"Europ.J.Neurosci.. 17. 287-297 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichisaka, S.et al.: "Activity-dependent changes in the Protein level of brain-derived neurotrophic factor but no change in other neurotrophins in the visual cortex of young and adult ferrets"Neuroscience. 117. 361-371 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akaneya, Y.et al.: "Low-frequency depression of synaptic responses recorded from rat visual cortex"Neuroscience. 117. 305-320 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jiang, B.et al.: "Long-term depression is not induced by low frequency stimulation in rat visual cortex in vivo : A possible preventing role of endogenous BDNF"J.Neurosci.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Salami, M.et al.: "Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex"Proc.Nat.Acad.Sci.USA. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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