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Behavioral and physiological roles of the striatal GABAergic interneuronal types

Research Project

Project/Area Number 16300102
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

KOBAYASHI Kazuto  Fukushima Medical University, School of Medicine, Professor, 医学部, 教授 (90211903)

Co-Investigator(Kenkyū-buntansha) 八十島 安伸  福島県立医科大学, 医学部, 講師 (00273566)
小林 憲太  福島県立医科大学, 医学部, 助手 (70315662)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywordsstriatum / interneuron / γ-amino butyric acid / neural circuitry / immunotoxin / parvalbumin / somatostatin / motor control / GABA性介在ニューロン / 薬物誘導 / 遺伝子改変マウス / イムノトキシン細胞標的法
Research Abstract

The striatum is a central structure of the basal ganglia neural circuitry that mediates a variety of brain functions including motor control, motor learning, and reward-associated behavior. It contains some GABAergic interneuronal types that are different in their morphology and electrophysiological property. However, the difference in their behavioral and physiological roles remains unknown. In the present study, we addressed to study the roles of two kinds of straital GABAergic interneuronal types containing somatostatin (SST) or parvalbumin (PVA). We utilized immunotoxin cell targeting to eliminate the specific neuronal type from the neural circuitry and studied the resultant phenotypic changes. To eliminate the striatal GABAergic interneurons containing SST, we generated the mutant mice in which the human interleukin-2 receptor a-subunit (IL-2Rα) gene cassette was introduced into the mouse preprosomatostatin gene locus. These mice were injected intrastriatally with the recombinant immunotoxin, and the number of target neurons were reduced in the mutants. Phenotypic analysis of the mutants indicated that the SST-containing GABAergic interneurons play an important role in suppression of spontaneous motor behavior. In addition, to eliminate the straital GABAergic interneurons containing PVA we tried to produce the mutant mice in which the human IL-2Rα cassette was introduced into the mouse PVA gene locus. The knock-in targeting vector was introduced into embryonic stem (ES) cells, and the cells carrying the targeted mutation were screened with PCR and southern blot hybridization. We succeeded in obtaining multiple ES cells carrying the targeted mutation. Using these cells we are planning to generate the knock-in mutant mice and perform immunotoxin cell targeting to elucidate the behavioral and physiological roles of the striatal GABAergic interneurons containing PVA.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (47 results)

All 2006 2005 2004

All Journal Article (46 results) Book (1 results)

  • [Journal Article] Separation of μ-opioid receptor desensitization and internalization : endogenous receptors in primary neuronal cultures2006

    • Author(s)
      Arttamangkul, S. et al.
    • Journal Title

      J. Neurosci. 26 (15)

      Pages: 4118-4125

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dynamic temporal and cell type-specific expression of Wnt signaling components in the developing midbrain2006

    • Author(s)
      Rawal, N. et al.
    • Journal Title

      Exp. Cell Res. 312 (9)

      Pages: 1626-1636

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease2006

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

      J. Neurochem. 97 (3)

      Pages: 675-686

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Decline of endogenous dopamine release in parkin-deficient mice revealed by ex vivo autoradiography2006

    • Author(s)
      Sato, S. et al.
    • Journal Title

      J. Neurosci. Res. 84

      Pages: 1350-1357

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bidirectional reguation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons2006

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      Eur. J. Neurosci. 24 (10)

      Pages: 2789-2800

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Separation of μ-opioid receptor desensitization and internalization : endogenous receptors in primary neuronal cultures2006

    • Author(s)
      Atttamangkul, S. et al.
    • Journal Title

      J.Neurosci. 26(15)

      Pages: 4118-4125

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dynamic temporal and cell type- specific expression of Wnt signaling components in the developing midbrain2006

    • Author(s)
      Rawal, N. et al.
    • Journal Title

      Exp.Cell Res. 312(9)

      Pages: 1626-1636

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease2006

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

      J.Neurochem. 97(3)

      Pages: 675-686

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Decline of endogenous dopamine release in parkin-deficient mice revealed by ex vivo autoradiography2006

    • Author(s)
      Sato, S. et al.
    • Journal Title

      J.Neurosci.Res. 84

      Pages: 1350-1357

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bidirectional regulation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons2006

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      Eur.J.Neurosci. 24(10)

      Pages: 2789-2800

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Separation of μ-opioid receptor desensitization and internalization : endogeneous receptors in primary neuronal cultures2006

    • Author(s)
      Arttamangkul, S. et al.
    • Journal Title

      J. Neurosci. 26(15)

      Pages: 4118-4125

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Dynamic temporal and cell type-specific expression of Wnt signaling components in the developing midbrain2006

    • Author(s)
      Rawal, N. et al.
    • Journal Title

      Exp. Cell Res. 312(9)

      Pages: 1626-1636

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Granulocyte-colony stimulating factor is neuroprotective in a model of Parkison's disease2006

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

      J. Neurochem. 97(3)

      Pages: 676-686

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Decline of endogeneous dopamine release in parkin-deficient mice revealed by ex vivo autoradiography2006

    • Author(s)
      Sato, S. et al.
    • Journal Title

      J. Neurosci. Res. 84

      Pages: 1350-1357

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bidirectional redguation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons2006

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      Eur. J. neurosci. 24(10)

      Pages: 2789-2800

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury2005

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

      J. Am. Soc. Nephrol. 16 (4)

      Pages: 1013-1023

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular genetics of tyrosine 3-monooxygenase and inherited diseases2005

    • Author(s)
      Kobayashi, K., Nagatsu, T
    • Journal Title

      Biochem. Biophy. Res. Commun. 38 (1)

      Pages: 267-270

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional properties of dopaminergic neurones in the mouse olfactory bulb2005

    • Author(s)
      Pignatelli, A. et al.
    • Journal Title

      J. Physiol. 564 (2)

      Pages: 501-514

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Use of TH-GFP transgenic mice as a source of identified dopaminergic neurons for physiological studies in postnatal cell culture2005

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      J. Neurosci. Methods 146 (1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury2005

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

      J.Amj.Soc.Nephrol. 16(4)

      Pages: 10130-1023

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular genetics of tyrosine 3-monooxygenase and inherited Diseases2005

    • Author(s)
      Kobayashi, K., Nagatsu, T.
    • Journal Title

      Biochem.Biophys.Res.Commun. 38(1)

      Pages: 267-270

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Functional properties of dopaminergic neurones in the mouse olfactory bulb2005

    • Author(s)
      Pignatelli, A. et al.
    • Journal Title

      J.Physiol. 564(2)

      Pages: 501-514

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Use of TH-GFP transgenic mice as a source of identified dopaminergic neurons for physiological studies in postnatal cell culture2005

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      J.Neurosci.Methods 146(1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Molecular genetics of tyrosine 3-monooxygenase and inherited diseases2005

    • Author(s)
      Kobayashi, K., Nagatsu, T
    • Journal Title

      Biochem.Biophy.Res.Commun. 38(1)

      Pages: 267-270

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury2005

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

      J.Am.Soc.Nephrol. 16・4(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Use of TH-GFP transgenic mice as a source of identified dopaminergic neurons for physiological studies in postnatal cell culture2005

    • Author(s)
      Jomphe, C. et al.
    • Journal Title

      J.Neurosci.Meth. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional properties of dopaminergic neurons in the mouse olfactory bulb2005

    • Author(s)
      Pignatelli, A. et al.
    • Journal Title

      J.Physiol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Survival of developing motor neurons by Rho GTPase signaling pathway through Rho-kinase2004

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

      J. Neurosci. 24 (14)

      Pages: 3480-3488

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of GABA_A receptor subunit variants in midbrain dopaminergic neurons2004

    • Author(s)
      Okada, H. et al.
    • Journal Title

      J. Neurochem. 89 (1)

      Pages: 7-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells2004

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

      Neurosci. Lett. 363 (1)

      Pages: 33-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice2004

    • Author(s)
      Matsushita, N. et al.
    • Journal Title

      J. Neurosci. Res. 78 (1)

      Pages: 7-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice2004

    • Author(s)
      Saino-Saito, S. et al.
    • Journal Title

      J. Comp. Neurol. 479 (4)

      Pages: 389-398

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Survival of developingmotor neurons by Rho GTPase signaling pathway through Rho-kinase2004

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

      J.Neurosci. 24(14)

      Pages: 3480-3488

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification of GABA_A Receptor subunit variants in midbrain dopaminergic neurons2004

    • Author(s)
      Okada, H. et al.
    • Journal Title

      J.Neurochem. 89(1)

      Pages: 7-14

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells2004

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

      Neurosci.Lett. 363(1)

      Pages: 33-37

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice2004

    • Author(s)
      Matsushita, N. et al.
    • Journal Title

      J.Neurosci.Res. 78(1)

      Pages: 7-15

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice2004

    • Author(s)
      Saino-Saito, S. et al.
    • Journal Title

      J.Comp.Neurol. 479(4)

      Pages: 389-398

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Survival of developing motor neurons by Rho GTPase signaling pathway through Rho-kinase2004

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

      J.Neurosci. 24・14

      Pages: 3480-3488

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of GABA_A receptor subunit variants in midbrain dopaminergic neurons2004

    • Author(s)
      Okada, H. et al.
    • Journal Title

      J.Neurochem. 89・1

      Pages: 7-14

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Isolation and transplantation of dopaminergic neurons generated from mouse embryonic stem cells2004

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

      Neurosci.Lett. 363・1

      Pages: 33-37

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice2004

    • Author(s)
      Matsushita, N. et al.
    • Journal Title

      J.Neurosci.Res. 78・1

      Pages: 7-15

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice2004

    • Author(s)
      Saino-Saito, S. et al.
    • Journal Title

      J.Comp.Neurol. 479・4

      Pages: 389-398

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 線条体投射路を介する新しい神経回路メカニズム2004

    • Author(s)
      佐野裕美, 小林和人
    • Journal Title

      Clinical Neuroscience 22・6

      Pages: 732-732

    • Related Report
      2004 Annual Research Report
  • [Journal Article] イムノトキシン細胞標的法:神経回路メカニズムの解析法2004

    • Author(s)
      小林和人
    • Journal Title

      脳21 7・2

      Pages: 195-200

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cre-loxPシステム:コンディショナルな遺伝子改変技術2004

    • Author(s)
      小林憲太, 小林和人
    • Journal Title

      脳21 7・3

      Pages: 312-315

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 神経系の機能再生へのアプローチ2004

    • Author(s)
      小林和人
    • Journal Title

      理学療法学 31・8

      Pages: 448-450

    • NAID

      110004013358

    • Related Report
      2004 Annual Research Report
  • [Book] The Primer on the Autonomic Nervous System2004

    • Author(s)
      Kobayashi, K., Nagatsu, T.
    • Total Pages
      459
    • Publisher
      Elsevier Academic Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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