2002 Fiscal Year Final Research Report Summary
Analysis of neuronal plasticity using temporally regulated conditional knockout mice
| Project/Area Number |
13680885
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | RIKEN |
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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)
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| Project Period (FY) |
2001 – 2002
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| Keywords | knockout mice / cerebellum / Purkinje cell / diphtheria toxin / neuronal circuit / eyeblink conditioning |
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| 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.
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[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)
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[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)
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