Intracellular Zn2+ Signaling in the Dentate Gyrus Is Required for Object Recognition Memory

The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn2+ signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn2+ levels were decreased by injection of clioquinol and N,N,N,N-tetrakis-(2-pyridylmethyl) ethylendediamine. To pursue the effect of the loss and/or blockade of Zn2+ signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 mu l), an intracellular Zn2+ chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn2+ signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca2+ signaling in the dentate molecular layer. In vivo dentate gyrus long-term potentiation (LTP) was affected under the local perfusion of the recording region (the dentate granule cell layer) with 0.1 mM ZnAF-2DA, but not with 1-10 mM CaEDTA, an extracellular Zn2+ chelator, suggesting that the blockade of intracellular Zn2+ signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn2+ signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression. (c) 2014 Wiley Periodicals, Inc.