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Molecular and cellular basis of synaptic function

Research Project

Project/Area Number 03304026
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Neurophysiology and muscle physiology
Research InstitutionGunma University

Principal Investigator

OZAWA Seiji  Gunma University, School of Medicine, Professor, 医学部, 教授 (40049044)

Co-Investigator(Kenkyū-buntansha) HIGASHI Hideho  Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (10098907)
TAKAHASHI Tomoyuki  Tokyo University, School of Medicine, Professor, 医学部, 教授 (40092415)
AKAIKE Noriko  Kyusyu University, School of Medicine, Professor, 医学部, 教授 (30040182)
ONODERA Kayoko  Tokyo University, School of Medicine, Lecture, 医学部, 講師 (00053091)
MISHINA Masayoshi  Niigata University, Institute of Brain Research, Professor, 脳研究所, 教授 (80144351)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 1993: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1991: ¥4,900,000 (Direct Cost: ¥4,900,000)
KeywordsSynapse / Glutamate receptor / NMDA / AMPA / Intracellular calcium / Transmitter release / cDNA cloning / Plastic change / CDNAクローニング / グリシン受容体 / 遺伝子クローニング / GABA受容体 / 長期増強 / 長期抑圧
Research Abstract

In this study, we investigated molecular and cellular basis of synaptic transmission in the three aspects, namely 1)molecular structure and electrophysiological properties of receptor channels, 2)regulation of calcium metabolism and its relation to transmitter release, and 3)mechanism of synaptic plasticity. The main results are as follows.
1.Molecular structure and functional properties of receptor channels
Mishina has identified four modulatory subunits (epsilon1-epsilon4)of the mouse NMDA receptor by cloning and expression of cDNAs. This molecular diversity of the epsilon subunits underlies the functional heterogeneityb of the NMDA receptor. Ozawa has coupled patch-clamp recordings and reverse transcription followed by PCR amplification, and identified the subunit composition of the Ca^<2+>-permeable AMPA receptor at the single cell level. Takahashi has expressed fetal- and adult-type glycine receptor cDNAs, and shown that the mean open time of the adult-type receptor has a shorter op … More en time. This result is consistent with that the decay time of glycinergic IPSCs becomes shorter during postnatal development.
2.Calcium metabolism and transmitter release
Kuba has measured intracellular Ca^<2+> concentration in sympathetic neurons and presented the evidence that the activation of calcium-induced calcium release occurs as a result of Ca^<2+>-influx through voltage-dependent Ca^<2+> channels. Yawo has shown that Ca^<2+>-influx through the N-type Ca^<2+> channel mediates transmitter release from the chick ciliary presynaptic terminal. Tachibana has demontrated that the transmitter of the ganglion cell of the goldfish retina is L-gluatamate, and that this transmitter release is mediated by the activation of L-type Ca^<2+> channels.
3.Mechanism of synaptic plasticity
Hirano has investigated the mechanism of long-term depression (LTD) of the synaptic transmission between cerebellar granule and Purkinje cells, presenting the evidence that the adtivation of metabotropic glutamate receptor (mGluR1) is involved in the induction of LTD. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (61 results)

All Other

All Publications (61 results)

  • [Publications] Bochet,P.et al.: "Subunit composition at the single cell level explains functional properties of a glutamate-gated channel." Neuron. in press. (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi,T.et al.: "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels." Neuron. 9. 1155-1161 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onodera,K.et al.: "Uneven distribution of excitatory amino acid receptors on ventral horn neurones of newborn rat spinal cord." Journal of Physiology. 439. 257-276 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akaike,N.et al.: "GABAergic synaptic current in dissociated nucleus basalis of Meynert neurons of the rat." Brain Research. 570. 102-108 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kutuwada,T.et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Higashi,H.et al.: "Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea pig cingulate cortical neurons." Neuroscience. 55. 129-138 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akasu,T.et al.: "Myosin light chain kinase occurs in bullfrog sympathetic neurons and may modulate voltage-dependent potassium currents." Neuron. 11. 1-13 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami,R.et al.: "A variant of metabotropic glutamate receptor subtype 5:an evolutionary conserved insertion with no termination codon." Biochem.Biophys.Res.Commun.194. 622-627 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hua,S.-Y.et al.: "Characteristics of Ca^<2+> release induced by Ca^<2+> influx in cultured bullfrog sympathetic neurones." Journal of Physiology. 464. 245-272 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tachibana,M.et al.: "Dihydropyridine-sensitive calcium current mediates neurotransmitter release from bipolar cells of the goldfish retina." Journal of Neuroscience. 13. 2898-2909 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yawo,H.et al.: "Preferential inhibition of ω-conotoxin-sensitive presynaptic Ca^<2+> channels by adenosine autoreceptors." Nature. 365. 256-258 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kudo,Y.et al.: "Heterogeneous disribution of fuctional glutamate receptor subtypes in organotypic slice culture of rat hippocampus revealed by calcium fluorometry." Bioimages. 1. 159-166 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirano,T.et al.: "Spatial distribution of excitatory and inhibitory synapses on a Purkinje cell in a rat cerebellar culture." Journal of Neurophysiology. 70. 1316-1325 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bochet, P.et al.: "Subunit composition at the single cell level explains functional properties of a glutamate-gated channel." Neuron. (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi, T.et al.: "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels." Neuron. 9. 1155-1161 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Onodera, K.et al.: "Uneven distribution of excitatory amino acid receptors on ventral hom neurones of newborn rat spinal cord." Journal of Physiology. 439. 257-276 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akaike, N.et al.: "GABAergic synaptic current in disociated nucleus basalis of Meynert neurons of the rat." Brain Research. 570. 102-108 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kutsuwada, T.et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Higashi, H.et al.: "Ionic mechanisms underlying the depolarizing and hyper polarizing afterpotentials of single spike in guinea pig cingulate cortical neurons." Neuroscience. 55. 129-138 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akasu, T.et al.: "Myosin light chain kinase occurs in bullfrog sympathetic neurons and ay modulate voltage-dependent potassium currents." Neuron. 11. 1-13 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Minakami, R.et al.: "A variant of metabotropic glutamate receptor subtype 5 : an evolutionary conserved insertion with no termination codon." Biochem.Biohys, Res.Commun.194. 622-627 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hua, S.-Y.et al.: "Characteristics of Ca^<2+> release induced by Ca^<2+> influx in cultured bullfrog sympathetic neurones." Journal of Physiology. 464. 245-272 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tachibana, M.et al.: "Dihydropyridine-sensitive calcium current mediates neurotransmitter release from bipolar cells of the goldfish retina." Journal of Neuroscience. 13. 2898-2909 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yawo, H.et al.: "Preferential inhibition of omega-conotoxin-sensitive presynaptic Ca^<2+> channels by adenosine autoreceptors." Nature. 365. 256-258 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kudo, Y.et al.: "Heterogeneous distribution of fuctional glutamate receptor subtypes in organotypic slice culture of rat hippocampus revealed by calcium fluorometry." Bioimages. 1. 159-166 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirano, T.et al.: "Spatial distribution of excitatory and inhibitory synapses on a Purkinje cell in a rat cerebellar culture." Journal of Neurophysiology. 70. 1316-1325 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Bochet,P.et al.,: "Subunit composition at the single cell level explains functional properties of a glutamate-gated channel." Neuron in press. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahashi,T.et al.,: "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels." Neuron. 9. 1155-1161 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Onodera,K.et al.: "Uneven distribution of excitatory amino acid receptors on ventral horn neurones of newborn rat spinal cord." Journal of Physiology. 439. 257-276 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akaike,N.et al.: "GABAergic synaptic current in dissociated nucleus basalis of Meynert neurons of the rat." Brain Research. 570. 102-108 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kutuwada,T.et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Higashi,H.et al.: "Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea pig cingulate cortical neurons." Neuroscience. 55. 129-138 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akasu,T.et al.: "Myosin light chain kinase occurs in bullfrog sympathetic neurons and may modulate voltage-dependent potassium currents." Neuron. 11. 1-13 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Minakami,R.et al.: "A variant of metabotropic glutamate receptor subtype 5:an evolutionary conserved insertion with no termination codon." Biochem.Biophys.Res.Commun.194. 622-627 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hua,S.-Y.et al.: "Characteristics of Ca^<2+> release induced by Ca^<2+> influx in cultured bullfrog sympathetic neurones." Journal of Physiology. 464. 245-272 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tachibana,M.et al.: "Dihydropyridine-sensitive calcium current mediates neurotransmitter release from bipolar cells of the goldfish retina." Journal of Neuroscience. 13. 2898-2909 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yawo,H.et al.: "Preferential inhibition of ω-conotoxin-sensitive presynaptic Ca^<2+> channels by adenosine autoreceptors." Nature. 365. 256-258 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kudo,Y.et al.: "Heterogeneous disribution of fuctional glutamate receptor subtypes in organotypic slice culture of rat hippocampus revealed by calcium fluorometry." Bioimages. 1. 159-166 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hirano,T.et al.: "Spatial distribution of excitatory and inhibitory synapses on a Purkinje cell in a rat cerebellar culture." Journal of Neurophysiology. 70. 1316-1325 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kutsuwada,t.et al.: "Molecular diversity of the NMDA recerpor channel." Nature. 358. 36-41 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsuzuki,K.et al.: "Agonist-and subunit-dependent poteniation of glutamate receptors by a nootropic drug aniracetam." Molecular brain Research. 16. 105-110 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Akaike,N.et al.: "GABAergic synaptic current in dissociated nucleus basalis of Mynert neurons of the rat." Brain Research. 570. 102-108 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Takahashi,T.et al.: "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels." Neuron. 9. 1155-1161 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ito,I.et al.: "3,5-Dihydroxyphenylglycine:a potent agonist of metabotropic glutamate receptors." NeuroReport.

    • Related Report
      1992 Annual Research Report
  • [Publications] Nohmi,M.et al.: "Basal Ca and the oscillation of Ca in caffeine-treated bull-frog sympathetic neurones." Journal of Physiology. 450. 513-528 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Yawo,H.et al.: "Re-evaluation of calcium currents in pre-and postsynaptic reurones of the chick ciliary ganglion." Journal of Physiology.

    • Related Report
      1992 Annual Research Report
  • [Publications] Okada,T. et al.: "Relationship between Ca current and intracellular Ca^<2+> concentration in bioplar cells isolated from the goldfish retina." Relationship between Ca current and intracellular CAaDtDtル2+aCtDtル concentration in bipolar cells isolated from the goldfish retina.

    • Related Report
      1992 Annual Research Report
  • [Publications] Kudo,Y.et al.: "A single optical fiber fluorometric device for measurement of intracellurar Ca^<2+> concentration:its application to hippocampal neurons in virto and in vivo." Neuroscience. 50. 619-625 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishimura,T.et al.: "Guanosine 3',5'-cyclic monophoshate regulates calcuim channels in neurones of rabbit vesical pelvic ganglia." Journal of Physiology. 457. 559-574 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mishina,M.et al.: "A single amino acid residue determines the Ca^<2+> permeability of AMPAーselective glutamate receptor channels." Biochem.Biophys.Res.Commun.180. 813-821 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ozawa,S.et al.: "Two types of kainate response in cultured rat hippocampal neurons." J.Neurophysiol.66. 2-11 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Onodera,K.et al.: "Uneven distubution of excitatory amino acid receptors on ventral horn neurones of newborn rat spinal cord." J.Physiol.439. 257-276 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Akaike,N.et al.: "GABAergic synaptic current in dissociated nucleus basalis of Meynert neurons of the rat." Brain Res.

    • Related Report
      1991 Annual Research Report
  • [Publications] Takahashi,T.et al.: "SingleーChannel currents underlying glycinergic inhibitory postsynaptic responses in spinal neurons." Neuron.

    • Related Report
      1991 Annual Research Report
  • [Publications] Higashi,H.et al.: "Synaptic responses of guinea pig cingulate cortical neurons in vitro." J.Neurophysiol.65. 822-833 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kuba,K.et al.: "Spatial and dynamic changes in intracellular Ca^<2+> measured by confocal laserーscanning microscopy in bullfrog sympathetic ganglion cells." Neurosci.Res.10. 245-259 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tokimasa,T.et al.: "Slowly inactivating potassium current in cultured bullーfrog primary afferent and sympathetic neurones." J.Physiol.435. 585-604 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tachibana,M.et al.: "Release of endogenous excitatory amino acids from ONーtype bipolar cells isolated from the goldfish retina." J.Neurosci.11. 2199-2208 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ito,I.et al.: "Roles of glutamate receptors in longーterm potentiation at hippocampal mossy fiber synapses." NeuroReport. 2. 333-336 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kudo,Y.et al.: "A “macro" image analysis of furaー2 fluorescence to visualize the distribution of functional glutamate receptor subtypes in hippocampal slices." Neurosci.Res.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirano,T.: "Differential preー and postsynaptic mechanisms for synaptic potentiation and depression between a granule cell and a Purkinje cell in rat cerebellar culture." Synapse. 7. 321-323 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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