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Molecular Neurobiology

, Volume 55, Issue 5, pp 3856–3865 | Cite as

Weakened Intracellular Zn2+-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP

  • Atsushi Takeda
  • Haruna Tamano
  • Taku Murakami
  • Hiroyuki Nakada
  • Tatsuya Minamino
  • Yuta Koike
Article

Abstract

Memory is lost by the increased influx of extracellular Zn2+ into neurons. It is possible that intracellular Zn2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn2+ dynamics was compared between young and aged rats. The influx of extracellular Zn2+ into dentate granule cells was increased in aged rats after injection of high K+ into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn2+ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn2+ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn2+, but not in young rats. Interestingly, the capacity of chelating intracellular Zn2+ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn2+-buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn2+ dynamics than in young rats, probably due to weakened intracellular Zn2+-buffering.

Keywords

Zn2+-buffering Dentate granule cell LTP maintenance AMPA receptor Aging 

Notes

Compliance with Ethical Standards

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 (approval numbers: 136043)

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Neurophysiology, School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan

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