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1996 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1994 – 1996
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.

  • Research Products

    (15 results)

All Other

All Publications (15 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-09  

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