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Genetic enhancement of learning and memory in mice

Author

Listed:
  • Ya-Ping Tang

    (Princeton University)

  • Eiji Shimizu

    (Princeton University)

  • Gilles R. Dube

    (The Center for Learning and Memory, MIT)

  • Claire Rampon

    (Princeton University)

  • Geoffrey A. Kerchner

    (School of Medicine, Washington University)

  • Min Zhuo

    (School of Medicine, Washington University)

  • Guosong Liu

    (The Center for Learning and Memory, MIT)

  • Joe Z. Tsien

    (Princeton University)

Abstract

Hebb's rule (1949) states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better learning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector1,2,3,4, acts as a graded switch for memory formation, enhanced signal detection by NMDA receptors should enhance learning and memory. Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10–100 Hz. These mice exhibit superior ability in learning and memory in various behavioural tasks, showing that NR2B is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA-receptor-dependent modifications of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible.

Suggested Citation

  • Ya-Ping Tang & Eiji Shimizu & Gilles R. Dube & Claire Rampon & Geoffrey A. Kerchner & Min Zhuo & Guosong Liu & Joe Z. Tsien, 1999. "Genetic enhancement of learning and memory in mice," Nature, Nature, vol. 401(6748), pages 63-69, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6748:d:10.1038_43432
    DOI: 10.1038/43432
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    Cited by:

    1. Karpinski, Ruth I. & Kinase Kolb, Audrey M. & Tetreault, Nicole A. & Borowski, Thomas B., 2018. "High intelligence: A risk factor for psychological and physiological overexcitabilities," Intelligence, Elsevier, vol. 66(C), pages 8-23.
    2. David M Santucci & Sridhar Raghavachari, 2008. "The Effects of NR2 Subunit-Dependent NMDA Receptor Kinetics on Synaptic Transmission and CaMKII Activation," PLOS Computational Biology, Public Library of Science, vol. 4(10), pages 1-16, October.
    3. Mégane Missaire & Nicolas Fraize & Mickaël Antoine Joseph & Al Mahdy Hamieh & Régis Parmentier & Aline Marighetto & Paul Antoine Salin & Gaël Malleret, 2017. "Long-term effects of interference on short-term memory performance in the rat," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-18, March.
    4. Yiu Chung Tse & Rosemary C Bagot & Juliana A Hutter & Alice S Wong & Tak Pan Wong, 2011. "Modulation of Synaptic Plasticity by Stress Hormone Associates with Plastic Alteration of Synaptic NMDA Receptor in the Adult Hippocampus," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-14, November.

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