Analysis of neuronal plasticity using temporally regulated conditional knockout mice

• Project/Area Number: 13680885
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: RIKEN
• Principal Investigator: IKEDA Toshio RIKEN, Laboratory for Behavioral Genetics, research specialist, 行動遺伝学技術開発チーム, 専門職研究員 (80252526)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000); Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: knockout mice / cerebellum / Purkinje cell / diphtheria toxin / neuronal circuit / eyeblink conditioning / 組換え / 運動学習 / Pou3fl遺伝子 / 前脳 / Cre recombinase / 回避学習 / 誘導型組換え / 合成ステロイド

Research Abstract

The cerebellum has an essential role in motor coordination and motor learning. To investigate the neural circuit underlying motor learning and the retention of motor memory, we developed a genetic cell-ablation system in the mouse. In this mouse, ligand-induced recombination results in preferential ablation of Purkinje cells. Along with the Purkinje cell loss, these mice exhibited dystonic movement of the feet, severe ataxia, and ligand-dependent impaired performance in the rotarod test. Eyeblink conditioning was analyzed to further address the role of Purkinje cells in motor learning and the expression of motor memory. In a delay paradigm (cerebellum-dependent associative learning), administration of ligand impaired acquisition of the conditioned response and expression of the acquired conditioned response. In a trace paradigm (hippocampus-dependent associative learning), the acquired conditioned response was also impaired after ligand administration. There was no obvious anatomic abnormality of the ponto-cerebellar pathway in ligand-administered mice. Furthermore, the mice had normal responses to aversive stimuli. These results suggest that Purkinje cells have a crucial role in cerebellar-dependent motor learning, the expression of motor memory, and in the performance of hippocampal-dependent associative motor memory.

Research Products

• [Publications] Michishita M et al.: "A novel gene, Bicl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain."Biochem Biophys Res Commun. 306. 680-686 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Li Q.-L.et al.: "Causal relationship between the loss of RUNX3 expression and gastric cancer.Cell."Cell. 109. 113-124 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nakashiba, T. et al.: "Complementary Expression and Neurite Outgrowth Activity of Netrin-G Subfamily Members."Mechanisms of Development. 111. 47-60 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Michishita M., Ikeda T., Nakashiba T., Ogawad M, Tashiroe T., Honjo T., Doi K., Itohara S., Endo S.: "A novel gene, Btcl1, encoding CUB and LDLa domains is expressed in restricted areas of mouse brain."Biochem Biophys Res Commun.. 306. 680-686 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Li Q.-L., Ito K., Sakakura C., Fukamachi H., Inoue K., Chi X.-Z., Lee K.-Y., Nomura S., Lee C.-W., Han S.-B., Kim H.-M., Kim W.-J., Yamamoto H., Yamashita N., Yano T., Ikeda T., Itohara S., Inazawa J., Abe T., Hagiwara A., Yamagishi H., Ooe A., Kaneda A., Sugimura T., Ushijima T., Bae S.-C., Ito Y.: "Causal relationship between the loss of RUNX3 expression and gastric cancer."Cell. 109. 113-124 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Toshiaki Nakashiba, Sachiko Nishimura, Toshio Ikeda, Shigeyoshi Itohara: "Complementary expression and neurite outgrowth activity of Netrin-G subfamily members."Mechanisms of Development. 111. 47-60 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] LiQ.-L.et al.: "Causal relationship between the loss of RUNX3 expression and gastric cancer"Cell. 109・1. 113-124 (2002)
• [Publications] Nakashiba, T. et al.: "Complementary Expression and Neurite Outgrowth Activity of Netrin-G Subfamily Members."Mechanisms of Development. 111. 47-60 (2002)
• [Publications] Toshiaki Nakashiba., Toshio Ikeda et al.: "Complementary Expression and Neurite Outgrowth Activity of Netrin-G Subfamily Members"Mechanisms of Development. 111. 47-60 (2002)