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Functional implication of transmitter switching of inhibitory Circuits.

Research Project

Project/Area Number 19390055
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

NABEKURA Junichi  National Institute for Physiological Sciences, 発達生理学研究系, 教授 (50237583)

Co-Investigator(Kenkyū-buntansha) ISHIBASHI Hitoshi  生理学研究所, 発達生理学研究系, 准教授 (50311874)
渡部 美穂  生理学研究所, 発達生理学研究系, 特任助教 (10399321)
高鶴 裕介  生理学研究所, 発達生理学研究系, 特別協力研究員 (30446265)
Co-Investigator(Renkei-kenkyūsha) WATANABE Miho  生理学研究所, 発達生理学研究系, 特任助教 (10399321)
TAKATSURU Yusuke  生理学研究所, 発達生理学研究系, 特別協力研究員 (30446265)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
KeywordsGABA / スイッチング / GABAB受容体 / グリシン / 外側上オリーブ核 / 発達 / シナプス / スイッチ / 聴覚 / パッチクランプ
Research Abstract

聴覚中継路である内側台形体核(NMTB)から外側上オリーブ核(LSO)への入力は発達とともにGABAからグリシンへスイッチする。今回、この伝達物質自体のスイッチングの生理学的意義を解明するために、未熟期におけるGABAB受容体の回路機能発達に対する役割を検討した。未熟期には神経終末から放出されるGABAによって終末に存在するGABAB受容体が活性化されるが、発達とともにLSO核からGABAB受容体の発現が消失した。GABAB受容体ノックアウト動物も用いて未熟期のみ発現するGABAB受容体の意義の解明を行った。生後3週目のGABABノックアウトマウスにおいては、NMTB-LSOシナプスにおいて、細胞間に入力様式のばらつきが確認された。この原因はノックアウトマウスではシナプス小胞の伝達放出効率のばらつきに起因することが示唆された。この結果から、幼若期にGABAである生理的な意義として、GABAによるGABAb受容体の活性化、これによる長期的な抑制性性伝達回路の入力の細胞間の均一化に寄与していることが示唆される。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (28 results)

All 2009 2008 2007

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (10 results)

  • [Journal Article] Resting microglia directly monitor the function al state of synapses in vivo and determine the fate of ischemic terminals.2009

    • Author(s)
      Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J
    • Journal Title

      J Neurosci 39

      Pages: 3974-3980

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of chloride outward transport by gadolinium in cultured rat spinal cord.2009

    • Author(s)
      Ishibashi H, Hirao K, Yamaguchi J, Nabekura J
    • Journal Title

      Neurotoxicology 30

      Pages: 155-159

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of chloride outward transport by gadolinium in cultured rat spinal cord neurons2009

    • Author(s)
      Ishibashi H, Hirao K, Yamaguchi J, Nabekura J
    • Journal Title

      Neurotoxicology 30

      Pages: 155-159

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sustained depolarizing shift of the GABA reversal potential by glutamate receptor activation in hippocampal neurons.2008

    • Author(s)
      Kitamura A, Ishibashi H, Watanabe M, Takatsuru Y, Brodwick M, Nabekura J
    • Journal Title

      Neurosci Res 62

      Pages: 270-277

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Stem Cell Source for Vasculogenesis in Ischemia : Subfraction of Side Population Cells from Dental Pulp.2008

    • Author(s)
      Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H, Nakamura H, Into T, Matsushita K, Nakashima M
    • Journal Title

      Stem Cell 26

      Pages: 2408-2418

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel stem cell source for vasculogenesis in ischemia : subfraction of side population cells from dental pulp2008

    • Author(s)
      Iohara K, Zheng L, Wake H, Ito M, Nabekura J, Wakita H, Nakamura H, Into T, Matsushita K, Nakashima M
    • Journal Title

      Stem Cells 26

      Pages: 2408-2418

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sustained depolarizing shift of the GABA reversal potential by glutamate receptor activation in hippocampal neurons2008

    • Author(s)
      Kitamura A, Ishibashi H, Watanabe M, Takatsuru Y, Brodwick M, Nabekura J.
    • Journal Title

      Neurosci Res 62

      Pages: 270-277

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effect of zinc on glycinergic inhibitory postsynaptic currents in rat spinal dorsal horn neurons.2007

    • Author(s)
      Eto K, Arimura Y, Nabekura J, Noda M, Ishibashi H
    • Journal Title

      Brain Res 1161

      Pages: 11-20

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Kv channel subtypes on GABA release in mechanically dissociated neurons from the rat substantia nigra.2007

    • Author(s)
      Shimada H, Uta D, Nabekura J, Yoshimura M
    • Journal Title

      Brain Res 1141

      Pages: 74-83

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of metabotropic glutamate receptor-mediated heterosynaptic inhibition of developing MNTB-LSO inhibitory synapses.2007

    • Author(s)
      Nishimaki T, Jang IS, Ishibashi H, Yamaguchi J, Nabekura J
    • Journal Title

      Eur J Neurosci 26

      Pages: 323-330

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] High potassium-induced facilitation of glycine release from presynaptic terminals on mechanically dissociated rat spinal dorsal horn neurons in the absence of extracellular calcium.2007

    • Author(s)
      Ishibashi H, Jang IS, Nabekura J
    • Journal Title

      Neuroscience 146

      Pages: 190-201

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Altered distribution of KCC2 in cortical dysplasia in patients with intractable epilepsy.2007

    • Author(s)
      Munakata M, Watanabe M, Otsuki T, Nakama H, Arima K, Itoh M, Nabekura J, Iinuma K, Tsuchiya S
    • Journal Title

      Epilepsia 48

      Pages: 837-844

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phospholipase C-related inactive protein is implicated inthe constitutive internalization of GABAA receptors mediated by clathrin and AP2 adaptor complex.2007

    • Author(s)
      Kanematsu T, Fujii M, Mizokami A, Kittler JT, Nabekura J, Moss SJ, Hirata M
    • Journal Title

      J Neurochem 101

      Pages: 898-905

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phosholipase C - Related Inactive Protein is involved in Trafficking of gamma2 Subunit Containing GABAA Receptor to Cell Surface.2007

    • Author(s)
      Mizokami A, Kanematsu Ti, Ishibashi H, Yamaguchi T, Tanida I, Takenaka K, Nakayama K, Fukami K, Takenawa T, Kominami E, Moss S, Yamamoto T, Nabekura J , Hirata H
    • Journal Title

      J Neurosci 27

      Pages: 1692-1701

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Early changes in KCC2 phosphorylation in response to neuronal stress results in functional downregulation.2007

    • Author(s)
      Wake H, Watanabe M, Moorhouse AJ, Kanematsu T, Horibe S, Matsukawa N, Asai K, Ojika K, Hirata M, Nabekura J
    • Journal Title

      J Neurosci 27

      Pages: 1642-1650

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Kv channel subtypes on GABA release in mechanically dissociated neurons from the rat substantia nigra2007

    • Author(s)
      Shimada H, Uta D, Nabekura J, Yoshimura M
    • Journal Title

      Brain Research 1141

      Pages: 74-83

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of metabotropic glutamate receptor-mediated heterosynaptic2007

    • Author(s)
      Nishimaki T, Jang IS, Ishibashi H, Yamaguchi J, Nabekura J
    • Journal Title

      European Journal of Neuroscience 26

      Pages: 323-330

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High potassium-induced facilitation of glycine release from presynaptic terminals on mechanically dissociated rat spinal dorsal hom neurons in the absence of extraceUular calcium2007

    • Author(s)
      Ishibashi H, Jang JS, Nabekura J.
    • Journal Title

      Neuroscience 146

      Pages: 190-201

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抑制性伝達物質スイッチングの機能的意義の解明2008

    • Author(s)
      山口純弥,石橋 仁,鍋倉淳一
    • Organizer
      第55回中部日本生理学会
    • Place of Presentation
      長久手町
    • Year and Date
      2008-10-17
    • Related Report
      2008 Final Research Report
  • [Presentation] カリウム-クロライド共役担体KCC2の機能発現制御. The role of tyrosine phosphorylation in regulation of neuron-specific K+-Clcotransporter, KCC2 in mature hippocampal neurons.2008

    • Author(s)
      渡部美穂, 和氣弘明, 鍋倉淳一
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-11
    • Related Report
      2008 Final Research Report
  • [Presentation] グルタミン酸刺激によるGABA 応答の変化2008

    • Author(s)
      石橋 仁, 北村明彦, 渡部美穂, Brodwick M, 鍋倉淳一
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-11
    • Related Report
      2008 Final Research Report
  • [Presentation] 抑制性シナプスにおける GABA/グリシンのスイッチングのメカニズム. Mechanisms underlying the switch from GABA to glycine release at inhibitory nerve terminals.2008

    • Author(s)
      山口純弥, 石橋 仁, 鍋倉淳一
    • Organizer
      第31回日本神経科学大会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-10
    • Related Report
      2008 Final Research Report
  • [Presentation] Physiological role of GABAB receptor at inhibitory synapses in developing LSO neurons.2008

    • Author(s)
      Nishimaki T, Jang IS, Ohno K, Nabekura J
    • Organizer
      The 38th Seiriken/Sokendai International Conference "Stock and flow of functional molecules in synapse"
    • Place of Presentation
      Okazaki
    • Year and Date
      2008-03-30
    • Related Report
      2008 Final Research Report
  • [Presentation] 抑制性シナプスにおけるGABA/グリシンのスイッチングメカニズム2008

    • Author(s)
      山口純弥, 石橋 仁, 鍋倉淳一
    • Organizer
      第85回生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-03-26
    • Related Report
      2008 Final Research Report
  • [Presentation] 発達期および障害回復期における神経回路再編成2008

    • Author(s)
      鍋倉淳一
    • Organizer
      自然科学研究機構シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2008-03-20
    • Related Report
      2008 Final Research Report
  • [Presentation] 抑制性シナプスにおけるGABA からグリシンへのスイッチングに関する電気生理学的研究2008

    • Author(s)
      石橋 仁, 山口純弥, 西巻拓也, 鍋倉淳一
    • Organizer
      第81回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2008-03-18
    • Related Report
      2008 Final Research Report
  • [Presentation] On the modulation of the chloride equilibrium potential following glutamate stimulation in hippocampal neurons.2007

    • Author(s)
      Kitamura A, Ishibashi H, Brodwick M, Nabekura J
    • Organizer
      The 37th Annual Meeting of the Society for Neuroscience ( ポスター発表)
    • Place of Presentation
      San Diego, California, USA
    • Year and Date
      2007-11-06
    • Related Report
      2008 Final Research Report
  • [Presentation] 高K+による神経終末部の脱分極は細胞外Ca2+に依存せずに神経伝達物質放出を増強する2007

    • Author(s)
      石橋 仁, 張 一成, 鍋倉淳一
    • Organizer
      第30回日本神経科学大会・ 第50回日本神経化学会大会・第17回日本神経回路学会大会、合同大会(Neuro 2007)(ポスター発表)
    • Place of Presentation
      横浜
    • Year and Date
      2007-09-11
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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