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  • The EMBO Journal (2000) 19, 2775 - 2785
  • doi:10.1093/emboj/19.12.2775

Impaired learning with enhanced hippocampal long-term potentiation in PTPdelta-deficient mice

Noriko Uetani1,2, Kunio Kato3, Hiro Ogura4, Kazuya Mizuno5, Kano Kawano4, Katsuhiko Mikoshiba3,6,7, Hidetaka Yakura5, Masahide Asano1,8 and Yoichiro Iwakura1

  1. Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
  2. Present address: Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo 183-8526, Japan
  3. Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, c/o Riken, Bunkyo-ku, Tokyo 113-0021, Japan
  4. Department of Neuroscience, Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Ibaraki 800-2635, Japan
  5. Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo 183-8526, Japan
  6. Department of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, 108-8639 Japan
  7. Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0193, Japan
  8. Present address: Institute for Experimental Animals, School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8640, Japan

Correspondence to:

Yoichiro Iwakura, E-mail: iwakura@ims.u-tokyo.ac.jp

Received 4 January 2000; Accepted 25 April 2000; Revised 11 April 2000

Protein tyrosine phosphatase delta (PTPdelta) is a receptor-type PTP expressed in the specialized regions of the brain including the hippocampal CA2 and CA3, B lymphocytes and thymic medulla. To elucidate the physiological roles of PTPdelta, PTPdelta-deficient mice were produced by gene targeting. It was found that PTPdelta-deficient mice were semi-lethal due to insufficient food intake. They also exhibited learning impairment in the Morris water maze, reinforced T-maze and radial arm maze tasks. Interestingly, although the histology of the hippocampus appeared normal, the magnitudes of long-term potentiation (LTP) induced at hippocampal CA1 and CA3 synapses were significantly enhanced in PTPdelta-deficient mice, with augmented paired-pulse facilitation in the CA1 region. Thus, it was shown that PTPdelta plays important roles in regulating hippocampal LTP and learning processes, and that hippocampal LTP does not necessarily positively correlate with spatial learning ability. To our knowledge, this is the first report of a specific PTP involved in the regulation of synaptic plasticity or in the processes regulating learning and memory.

  • Keywords:

    • learning,
    • long-term potentiation,
    • semi-lethality,
    • synaptic plasticity,
    • tyrosine phosphatase