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Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx

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Abstract

The idea that maintained LTP and memory are lost by either increase in intracellular Zn2+ in dentate granule cells or increase in intracellular Ca2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K+ into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K+-induced increase in intracellular Zn2+ but not high K+-induced increase in intracellular Ca2+. High K+-induced disturbances of LTP and intracellular Zn2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn2+, but not increase in intracellular Ca2+. NMDA and glucocorticoid, which induced Zn2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca2+ influx.

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Authors and Affiliations

  1. Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Atsushi Takeda, Haruna Tamano, Marie Hisatsune, Taku Murakami, Hiroyuki Nakada & Hiroaki Fujii

Authors
  1. Atsushi Takeda
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  2. Haruna Tamano
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  3. Marie Hisatsune
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  4. Taku Murakami
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  5. Hiroyuki Nakada
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  6. Hiroaki Fujii
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Corresponding author

Correspondence to Atsushi Takeda.

Ethics declarations

All the experiments were performed in accordance with the Guidelines for the Care and Use of Laboratory Animals of the University of Shizuoka that refer to the American Association for Laboratory Animals Science and the guidelines laid down by the NIH (NIH Guide for the Care and Use of Laboratory Animals) in the USA. The Ethics Committee for Experimental Animals in the University of Shizuoka has approved this work.

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The authors declare that they have no conflict of interest.

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Takeda, A., Tamano, H., Hisatsune, M. et al. Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx. Mol Neurobiol 55, 1498–1508 (2018). https://doi.org/10.1007/s12035-017-0428-3

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  • DOI: https://doi.org/10.1007/s12035-017-0428-3

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