• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The role of ambient GABA in cerebelllar foliation

Research Project

Project/Area Number 23500444
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokoha University (2013)
Hamamatsu University School of Medicine (2011-2012)

Principal Investigator

KUMADA Tatsuro  常葉大学, 保健医療学部, 教授 (00402339)

Co-Investigator(Renkei-kenkyūsha) FUKUDA Atsuo  浜松医科大学, 医学部, 教授 (50254272)
INOUE Koichi  浜松医科大学, 医学部, 准教授 (80345818)
Research Collaborator FURUKAWA Tomonori  浜松医科大学, 医学部, 技術補佐員 (60402369)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords小脳 / 細胞外GABA / GABAA受容体 / 小脳顆粒細胞 / 小脳皮質 / 葉形成 / GABA / 細胞分裂 / 神経発生
Research Abstract

Although distribution of GABA-A receptors and GABA-A receptor-mediated responses (excitability) are dynamically changed during stages of cerebellar morphogenesis, its roles on foliation and lobulation of cerebellar cortex have still remained unknown. Here, we addressed this issues by using various imaging methods and in vivo blockade experiments. Optical imaging method of extracellular GABA linked to enzymatic reaction of GABase enabled us to show temporal abundance of ambient GABA in the outer EGL region which have Granule precursor cells (GPCs). We also show that in vivo blockade of GABA-A receptor perturb the proliferation of these GPCs in the the posterior vermis of the early neonatal cerebellum. Furthermore, we have investigated the interaction between GABA-A receptor and sonic hedgehog (SHH) singlings by histochemical and Calcium imaging technique and suggested that SHH signalings seemed not to affect the GABA-A receptor-mediated responses.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (55 results)

All 2014 2013 2012 2011

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (33 results) Book (10 results)

  • [Journal Article] Activity-dependent endogenous taurine release facilitates excitatory neurotransmission in the neocortical marginal zone of neonatal rats.2014

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

      Front Cell Neurosci.

      Volume: 8 Pages: 33-33

    • DOI

      10.3389/fncel.2014.00033

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accumulation of GABAergic neurons, causing a focal ambient GABA gradient, and downregulation of KCC2 are induced during microgyrus formation in a mouse model of polymicrogyria2014

    • Author(s)
      Wang, T., Kumada, T., Morishima, T., Iwata, S., Kaneko, T., Yanagawa, Y., Yoshida, S. and Fukuda, A
    • Journal Title

      Cereb. Cortex

      Volume: 24 Pages: 1088-1101

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy2013

    • Author(s)
      Nakamura, K., Kodera, H., Akita, T., Shiina, M., Kato, M., Hoshino, H., Terashima, H., Osaka, H., Nakamura, S., Tohyama, J., Kumada, T., Furukawa, T., Iwata, S., Shiihara, T., Kubota, M., Miyatake, S., Koshimizu, E., Nishiyama, K., Nakashima, M., Tsurusaki, Y., Miyake, N., Hayasaka, K., Ogata, K., Fukuda, A., Matsumoto, N., and Saitsu, H
    • Journal Title

      Am. J. Hum. Genet

      Volume: 93 Pages: 496-505

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pre- and post-synaptic switches of GABA actions associated with Cl- homeostatic changes are induced in the spinal nucleus of the trigeminal nerve in a rat model of trigeminal neuropathic pain2013

    • Author(s)
      Wei, B., Kumada, T., Furukawa, T., Inoue, K., Watanabe, M., Sato, K. and Fukuda, A
    • Journal Title

      Neuroscience

      Volume: 228 Pages: 334-348

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] De Novo Mutations in GNAO1, Encoding a Gαo Subunit of Heterotrimeric G Proteins, Cause Epileptic Encephalopathy.2013

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

      Am. J. Hum. Genet.

      Volume: 93 Issue: 3 Pages: 496-505

    • DOI

      10.1016/j.ajhg.2013.07.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of GABAergic neurons, causing a focal ambient GABA gradient, and downregulation of KCC2 are induced during microgyrus formation in a mouse model of polymicrogyria.2013

    • Author(s)
      Wang T, Kumada T, Morishima T, Kaneko T, Yanagawa Y, Yoshida S, Fukuda A
    • Journal Title

      Cerebral Cortex

      Volume: in press Issue: 4 Pages: 1088-1101

    • DOI

      10.1093/cercor/bhs375

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of GABAergic neurons, causing a focal ambient GABA gradient, and downregulation of KCC2 are induced during microgyrus formation in a mouse model of polymicrogyria.2013

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

      Cereb. Cortex

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Guidepost neurons for the lateral olfactory tract : Expression of metabotropic glutamate receptor 1 and innervation by glutamatergic olfactory bulb axons2012

    • Author(s)
      Hirata, T., Kumada, T., Kawasaki, T., Furukawa, T., Aiba, A., Conquet, F., Saga, Y. and Fukuda, A
    • Journal Title

      Dev. Neurobiol

      Volume: 72 Pages: 1559-1576

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Taurine inhibits the K+-Clcotransporter KCC2 to regulate embryonic Cl- homeostasis via the with-no-lysine (WNK) protein kinase signaling pathway2012

    • Author(s)
      Inoue, K., Furukawa, T., Kumada, T., Yamada, J., Wang, T., Inoue, R. and Fukuda, A
    • Journal Title

      J. Biol. Chem

      Volume: 287 Pages: 20839-20850

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pre- and post-synaptic switches of GABA actions associated with Cl - homeostatic changes are induced in the spinal nucleus of the trigeminal nerve in a rat model of trigeminal neuropathic pain.2012

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

      Neuroscience

      Volume: 228 Pages: 334-348

    • DOI

      10.1016/j.neuroscience.2012.10.043

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Taurine inhibits K^+-Cl^- cotransporter KCC2 to regulate embryonic Cl^- homeostasis via with-no-lysine (WNK) protein kinase signaling pathway2012

    • Author(s)
      Inoue K, Furukawa T, Kumada T, Yamada J, Wang T, Inoue R, Fukuda A
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 25 Pages: 20839-20850

    • DOI

      10.1074/jbc.m111.319418

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Guidepost neurons for the lateral olfactory tract : expression of metabotropic glutamate receptor 1 and linnervation by glutamatergic olfactory bulb axons2012

    • Author(s)
      Hirata, T., Kumada, T., Kawasaki, T., Furukawa, T., Aiba, A., Conquet, F., Saga, Y. and Fukuda, A.
    • Journal Title

      Dev. Neurobiol

      Volume: (in press) Issue: 12 Pages: 1559-1576

    • DOI

      10.1002/dneu.22030

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Regional difference in GABA_A Receptor Mediated Ca^<2+> responses of radially migrating neurons in the mouse embryonic neocortex2013

    • Author(s)
      Kumada, T., Nakanishi, Y., Furukawa, T. and Fukuda, A
    • Organizer
      The 23th CDB meeting
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] 大脳皮質の発生過程における移動神経細胞の領域特異的なGABA_A受容体応答2013

    • Author(s)
      熊田竜郎, 中西康彦, 古川智範, 福田敦夫
    • Organizer
      第40回日本脳科学学会
    • Place of Presentation
      浜松
    • Related Report
      2013 Final Research Report
  • [Presentation] Activity dependent release of taurine facilitates the excitatory neurotransmission in the marginal zone of developing cerebral cortex2013

    • Author(s)
      Kumada, T., Qian, T., Nakamura, M., Furukawa, T., Yamada, J., Akita, T., Kilb, W., Luhmann, H.J., Nakahara, D. and Fukuda, A
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス大脳皮質の移動神経細胞における領域特異的なGABA_A受容体応答. 文部科学省科学研究費補助金「新学術領域・動く細胞と秩序」2013

    • Author(s)
      熊田竜郎
    • Organizer
      第7回領域班会議
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 活動依存的な内因性タウリンの放出が新生ラット大脳新皮質辺縁帯の興奮性シナプス伝達を促進する2013

    • Author(s)
      熊田竜郎, 千 太哲, 中村直人, 古川智範, Werner Kilb. Heiko J Luhmann. 中原大一郎, 福田敦夫
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス大脳皮質の移動神経細胞における領域特異的なGABA_A¥受容体応答2013

    • Author(s)
      熊田竜郎
    • Organizer
      冬の班会議
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス大脳皮質の移動神経細胞における領域特異的なGABAA受容体応答2013

    • Author(s)
      熊田竜郎
    • Organizer
      文部科学省科学研究費補助金「新学術領域・動く細胞と秩序」第7回領域班会議
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経活動依存的に放出されるタウリンは大脳皮質の辺縁帯における興奮性の神経伝達を促進する2013

    • Author(s)
      熊田竜郎
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 大脳皮質の発生過程における移動神経細胞の領域特異的なGABAA受容体応答2013

    • Author(s)
      熊田竜郎
    • Organizer
      第40回日本脳科学学会
    • Place of Presentation
      浜松
    • Related Report
      2013 Annual Research Report
  • [Presentation] Activity-dependent endogenous taurine release facilitates the excitatory neurotransmission in the neocortical marginal zone of neonatal rats.2013

    • Author(s)
      熊田竜郎ら
    • Organizer
      第90 回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Regional difference in GABA A Receptor Mediated Ca2+ responses of radially migrating neurons in the mouse embryonic neocortex.2013

    • Author(s)
      Kumada, T., et al,
    • Organizer
      The 23th CDB meeting, "Building multicellular systems from Cellular Cross-Talk"
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Pre- and post-synaptic switches of GABA actions in the spinal nucleus of the trigeminal nerve in a rat model of trigeminal neuropathic pain2012

    • Author(s)
      Kumada, T., Wei, B., Furukawa, T., Inoue, K., Watanabe, M., Sato, K. and Fukuda, A
    • Organizer
      The 12th Kyungpook-Hamamatsu Joint Medical Symposium Hamamatsu Meeting
    • Place of Presentation
      Hamamatsu, Japan
    • Year and Date
      2012-09-26
    • Related Report
      2013 Final Research Report
  • [Presentation] Intracellular taurine inhibits the functioning of KCC2 protein by phosphorylation via with-no-lysine (WNK) protein kinase pathway2012

    • Author(s)
      Fukuda, A., Inoue, K., Furukawa, T., Yamada, J., Kumada, T., Wang, T. and Inoue, R
    • Organizer
      The 8th FENS Forum of Neuroscience
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Final Research Report
  • [Presentation] 活動依存的な内因性タウリンの放出が新生ラット大脳新皮質辺縁体の興奮性シナプス伝達を促進する2012

    • Author(s)
      熊田竜郎, 千太哲, 中村直人, 古川智範, Kilb Werner, Luhmann Heiko J., 中原大一郎, 福田敦夫
    • Organizer
      生理学研究所研究会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス大脳皮質の移動神経細胞における領域特異的なGABA_A受容体応答2012

    • Author(s)
      熊田竜郎, 中西康彦, 古川智範, 江川潔, 福田敦夫
    • Organizer
      第59回中部生理学会
    • Place of Presentation
      岡崎
    • Related Report
      2013 Final Research Report
  • [Presentation] 胎仔脳の移動細胞におけるカルシウム振動の領域による相違2012

    • Author(s)
      熊田竜郎, 中西康彦, 古川智範, 江川潔, 福田敦夫
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 発達期大脳皮質における細胞外GABA とタウリンの分布の違いとそれに伴う移動神経細胞の異なるGABAA受容体応答2012

    • Author(s)
      熊田竜郎
    • Organizer
      平成24年度新学術領域「動く細胞と場のクロストークによる秩序の生成」夏の班会議
    • Place of Presentation
      神奈川
    • Related Report
      2013 Final Research Report
  • [Presentation] タウリン-WNK-SPAK/OSR1 シグナルによる神経特異的イオン輸送体KCC2の活性制御と大脳皮質構築への影響の検討2012

    • Author(s)
      井上浩一, 古川智範, 熊田竜郎, 福田敦夫
    • Organizer
      平成24年度新学術領域 「神経細胞の多様性と大脳新皮質の構築」夏の班会議
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] 胎仔脳の移動細胞におけるカルシウム振動の領域による相違2012

    • Author(s)
      中西康彦, 熊田竜郎, 古川智範, 江川潔, 福田敦夫
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞内タウリンによるKCC2 蛋白活性のリン酸化を介した修飾2012

    • Author(s)
      福田敦夫, 井上浩一, 古川智範, 山田順子, 熊田竜郎, 王 天英, 井上利恵子
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Related Report
      2013 Final Research Report
  • [Presentation] 活動依存的な内因性タウリンの放出が新生ラット大脳新皮質辺縁帯の興奮性シナプ ス伝達を促進する2012

    • Author(s)
      熊田竜郎ら
    • Organizer
      生理学研究所研究会「神経シナプス伝達の時空間ダイナミクス」
    • Place of Presentation
      岡崎
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス大脳皮質の移動神経細胞における領域特異的なGABA A受容体応答2012

    • Author(s)
      熊田竜郎ら
    • Organizer
      第59回中部生理学会
    • Place of Presentation
      岡崎
    • Related Report
      2012 Research-status Report
  • [Presentation] Pre- and post-synaptic switches of GABA actions in the spinal nucleus of the trigeminal nerve in a rat model of trigeminal neuropathic pain.2012

    • Author(s)
      Kumada, T., et al,
    • Organizer
      第12回慶北-浜松合同医学シンポジウム
    • Place of Presentation
      浜松
    • Related Report
      2012 Research-status Report
  • [Presentation] Regional difference in calcium oscillation of radially migrating neurons in the mouse embryonic neocortex.2012

    • Author(s)
      熊田竜郎ら
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Intracellular taurine inhibits the functioning of KCC2 protein by phosphorylation via with-no-lysine (WNK) protein kinase pathway.2012

    • Author(s)
      Fukuda, A., et al,
    • Organizer
      8th FENS Forum of Neuroscience
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2012 Research-status Report
  • [Presentation] Intracellular taurine modulates KCC2 function by phosphorylation.2012

    • Author(s)
      Fukuda, A., et al,
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Related Report
      2011 Research-status Report
  • [Presentation] Regionally differential calcium oscillation of radially migrating cells in embryonic cortex.2012

    • Author(s)
      Nakanishi, Y., et al,
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      長野
    • Related Report
      2011 Research-status Report
  • [Presentation] Taurine prevents KCC2 from functioning in a phosphorylation-dependent manner to render embryonic Cl- homeostasis2011

    • Author(s)
      Inoue, K., Furukawa, T., Yamada, J., Kumada, T., Wang, T., Inoue, R. and Fukuda, A
    • Organizer
      41st Annual Meeting, Society for Neuroscience
    • Place of Presentation
      Washington, D.C., USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 発達期大脳皮質における細胞外GABA とタウリンの分布の違いとそれに伴う移動神経細胞の異なるGABA_A受容体応答2011

    • Author(s)
      熊田竜郎
    • Organizer
      平成23年度新学術領域「動く細胞と場のクロストークによる秩序の生成」の班会議
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Temporal paracrine GABA and KCC2 downregulation underlie the formation of microgyrus in a model of focal cortical malformation2011

    • Author(s)
      Fukuda, A., Wang, T., Kumada, T., Morishima, T. and Yanagawa, Y
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 実験的皮質形成異常の成因におけるパラクリンGABA とKCC2発現抑制の役割2011

    • Author(s)
      福田敦夫, 王 天英, 熊田竜郎, 森島寿貴, 柳川右千夫
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Ambient GABA released from Bergmann glial cells promotes proliferation of cerebellar granule cell precursors.2011

    • Author(s)
      Fukuda, A., et al,
    • Organizer
      41st Annual Meeting, Society for Neuroscience.
    • Place of Presentation
      Washington, D.C.
    • Related Report
      2011 Research-status Report
  • [Presentation] Taurine prevents KCC2 from functioning in a phosphorylation-dependent manner to render embryonic Cl- homeostasis.2011

    • Author(s)
      Inoue, K., et al.,
    • Organizer
      41st Annual Meeting, Society for Neuroscience.
    • Place of Presentation
      Washington, D.C.
    • Related Report
      2011 Research-status Report
  • [Book] 脳科学辞典2013

    • Author(s)
      秋田天平, 熊田竜郎, 福田敦夫
    • Publisher
      塩素チャネル
    • Related Report
      2013 Final Research Report
  • [Book] Multimodal GABA_A Receptor Functions on Cell Development. In : Comprehensive Developmental Neuroscience (Rubenstein, J., Rakic, P., eds)2013

    • Author(s)
      Fukuda, A., Nakanishi, Y., Kumada, T., and Furukawa. T
    • Publisher
      Oxford : Elsevier
    • Related Report
      2013 Final Research Report
  • [Book] Migration in the cerebellum. In : Comprehensive Developmental Neuroscience "Cellular Migration and Formation of Neuronal Connections2013

    • Author(s)
      Komuro, Y., Kumada, T., Ohno, N., Foote, K. D., and Komuro, H
    • Publisher
      Oxford : Elsevier
    • Related Report
      2013 Final Research Report
  • [Book] Cerebellar patterning. In : Comprehensive Developmental Neuroscience, "Patterning and Cell Type Specification in the Developing CNS and PNS"2013

    • Author(s)
      Fahrion, J. K., Komuro, Y., Ohno, N., Littner, Y., Nelson, C., Kumada, T., Lamb, B., and Komuro, H
    • Publisher
      Oxford : Elsevier
    • Related Report
      2013 Final Research Report
  • [Book] Migration in the cerebellum. In: Comprehensive Developmental Neuroscience “Cellular Migration and Formation of Neuronal Connections2013

    • Author(s)
      Komuro, Y. et al.,
    • Total Pages
      17
    • Publisher
      Oxford: Elsevier
    • Related Report
      2013 Annual Research Report
  • [Book] Cerebellar patterning. In: Comprehensive Developmental Neuroscience, “Patterning and Cell Type Specification in the Developing CNS and PNS”2013

    • Author(s)
      Fahrion, J. K.,et al.,
    • Total Pages
      13
    • Publisher
      Oxford: Elsevier
    • Related Report
      2013 Annual Research Report
  • [Book] Granule Cell Migration and Differentiation, Handbook of the Cerebellum and Cerebellar Disorders, Chapter 112012

    • Author(s)
      Komuro, Y., Fahrion, J. F., Foote, K.D., Fenner K. B., Kumada, T., Ohno, N., and Komuro, H
    • Related Report
      2013 Final Research Report
  • [Book] Handbook of the Cerebellum and Cerebellar Disorders.2012

    • Author(s)
      Komuro, Y., et al,
    • Total Pages
      19
    • Publisher
      Granule Cell Migration and Differentiation.
    • Related Report
      2012 Research-status Report
  • [Book] Comprehensive Developmental Neuroscience.2012

    • Author(s)
      Fukuda, A., et al,
    • Publisher
      Elsevier
    • Related Report
      2011 Research-status Report
  • [Book] Neuronal cell migration in fetal alcohol syndrome. Handbook of Behavior, food and Nutrition, Chapter 1822011

    • Author(s)
      Kumada, T., Komuro, Y., Li, Y., Littner, Y., and Komuro, H
    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi