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Studies of neural functions of the higher animals by the gene targeting analyzes

Research Project

Project/Area Number 06454707
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SUGIYAMA Hiroyuki  Kyushu University, Faculty of Science, Department of Biology, Professor, 理学部, 教授 (20124224)

Co-Investigator(Kenkyū-buntansha) ITO Isao  Kyushu University, Faculty of Science, Department of Biology, Associate Professo, 理学部, 助教授 (20183741)
水上 令子  九州大学, 理学部, 助手 (00239302)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1996: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsgene targeting / glutamate receptor / long-term potentiation / NMDA receptor / learning / memory
Research Abstract

The goal of this project is to analyze the molecular mechanisms of neural fuctions of the higher animals (mice) by the method of targeted disruption of the genes for important neuronal molecules. Especially glutamate receptors of the NMDA type were focused, and the mice lacking the receptor subuints were examined (collaboration with Dr.Mishina, Tokyo University).
1.When the gene for the NMDA receptor epsilon1 subunit was disrupted in the mice, the long-term potentiation (LTP) in the CA1 region of hippocampal slices was significantly reduced. The mutant mice also showed reduced ability for the spatial learning. The results strongly suggested that the hippocampal LTP may be an important basis for the learning and memory.
2.The effects of the e1 disruption were studied during the postnatal development of the mice. NMDA receptor channel currents decreased with the age in both wild-type and mutant mice, but the values in the mutant mice were approximately half of those of the wild-type mice at all ages examined. In contrast, the LTP in the mutant mice was reduced in an age-dependent manner. The reduction was marginal at the neonate, and became progressively prominent, with the potentiation being 26% of that of the wild-type mice at the adulthood.
3.The effects of the epsilon1 disruption and the epsilon2 (another NMDA receptor subunit) disruption were compared at two distinct synaptic inputs in individual neurons in the CA3 region of hippocampal slices. The two types of gene disruptions caused different effects at the two synapses, suggesting that NMDA receptors with different subunit compositions may function in different synapses within a single CA3 pyramidal neuron.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Sakimura,K.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minakami,R.: "The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development." J.Neurochem.65. 1536-1542 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,I.: "Age-dependent reductuion of hippocampal LTP in mice lacking NMDA receptor ε1 subunit." Neurosci.Lett.203. 69-71 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura,K.: "Importance of N-terminal regions of G protein α subunits for the activation of phospholipase C in Xenpus oocytes." J.Biochem.(Tokyo). 120. 996-1001 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J.Physiol.(Lond.). (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 水上令子: "メタボトロピック受容体" 蛋白質核酸酵素. 42. 295-301 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fuji,K.: "Differential selectivity of M1 and M3 type muscarinic acetyocholine receptors in coulping with a G protein Gola examined in Xenopus oocytes" Neurosci.Lett.215. 131-133 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamashita,S.: "A Ga protein GL2a improves the ability to detect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes" Jpn.J.Physiol.47(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sakimura, K.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon1 subunit." Nature. 373. 151-155 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Minakami, R.: "The expression of two splice variants of metabotropic glutamate receptor subtype 5 in the rat brain and neuronal cells during development" J.Neurochem. 65. 1536-1542 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito, I.: "Age-dependent reductuion of hippocampal LTP in mice lacking NMDA receptor epsilon1 subunit." Neurosci.Lett.203. 69-71 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujii, K.: "Differential selectivity of M1 and M3 type muscarinic acetyocholine receptors in coulping with a G protein Go1alpha examined in Xenopus oocytes." Neurosci.Lett.215. 131-133 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nakamura, K.: "Importance of N-terminal regions of G protein alpha subunits for the activation of phospholipase C in Xenpus oocytes." J.Biochem. (Tokyo). 120. 996-1001 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamashita, S.: "A Galpha protein GL2alpha improves the ability to detect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes." Jpn.J.Physiol.47(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito, I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor epsilon1 or epsilon2 subunit." J.Physiol. (Lond.). (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito,I.: "Age-dependent reductuion of hippocampal LTP in mice lacking NMDA receptor ε1 subuint." Neurosci.Lett.203. 69-71 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujii,K.: "Differential selectivity of M1 and M3 type muscarinic acetyocholine receptors in coulping with a G protein Go1 α examined in Xenopus oocytes." Neurosci.Lett.215. 131-133 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura,K.: "Importance of N-terminal regions of G protein α subunits for the activation of phospholipase C in Xenpus oocytes." J.Biochem.(Tokyo). 120. 996-1001 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamashita,S.: "A G α protein GL2 α improves the ability to detect the subthreshold expressions of receptors linked to phospholipase C in Xenopus oocytes." Jpn.J.Physiol.47(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ito,I.: "Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA receptor ε1 or ε2 subunit." J.Physiol.(Lond.). (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 水上令子: "メタボトロピック受容体." 蛋白質核酸酵素. 42. 295-301 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Minakami, R.: "The expression of two splice variants of metabotropic glutamatereceptor subtype 5 in the rat brain and neuronal cells during development." J. Neurochem.65. 1536-1542 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakimura, K.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit" Nature. 373. 151-155 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ito, I.: "Age-dependent reductuion of hippocampal LTP in mice lackin NMDA receptor ε1 subuint" Neurosci. Lett.203. 69-71 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 杉山博之: "メタボトロピック・グルタミン酸受容体の特性と海馬シナプスにおける役割" 日本生理学雑誌(J. Physiol. Soc. Jpn.). 57. 253-260 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nakamura,K.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamate receptors in frog oocytes." J.Physiol.(Lond.). 474. 35-41 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sugiyama,H.: "Molecular and functional properties of metabotropic glutamate receptors in the brain." Biomed.Res.15. 29-31 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Minakami,R.: "Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5." Biochem.Biophys.Res.Commun.199. 1136-1143 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kasahara,J.: "Inositol phospholipid metabolism in Xenopus oocytes mediated by endogenous Go and Gi proteins." FEBS Lett.355. 41-44 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Sakimura,K.: "Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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