Takeda Atsushi, Tamano Haruna, Ogawa Taisuke, Takada Shunsuke, Nakamura Masatoshi, Fujii Hiroaki, Ando Masaki
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan; Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Hippocampus. 2014 Nov;24(11):1404-12. doi: 10.1002/hipo.22322. Epub 2014 Jul 4.
The role of perforant pathway-dentate granule cell synapses in cognitive behavior was examined focusing on synaptic Zn(2+) signaling in the dentate gyrus. Object recognition memory was transiently impaired when extracellular Zn(2+) 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 Zn(2+) signaling in dentate granule cells, ZnAF-2DA (100 pmol, 0.1 mM/1 µl), an intracellular Zn(2+) chelator, was locally injected into the dentate molecular layer of rats. ZnAF-2DA injection, which was estimated to chelate intracellular Zn(2+) signaling only in the dentate gyrus, affected object recognition memory 1 h after training without affecting intracellular Ca(2+) 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 Zn(2+) chelator, suggesting that the blockade of intracellular Zn(2+) signaling in dentate granule cells affects dentate gyrus LTP. The present study demonstrates that intracellular Zn(2+) signaling in the dentate gyrus is required for object recognition memory, probably via dentate gyrus LTP expression.
研究聚焦于齿状回中的突触锌离子信号传导，探讨了穿通通路-齿状颗粒细胞突触在认知行为中的作用。注射氯碘羟喹和N,N,N',N'-四（2-吡啶甲基）乙二胺降低细胞外锌离子水平后，物体识别记忆出现短暂受损。为了探究齿状颗粒细胞中锌离子信号传导缺失和/或阻断的影响，将细胞内锌离子螯合剂ZnAF-2DA（100皮摩尔，0.1毫摩尔/1微升）局部注射到大鼠齿状分子层。估计仅螯合齿状回中细胞内锌离子信号传导的ZnAF-2DA注射，在训练后1小时影响物体识别记忆，而不影响齿状分子层中的细胞内钙离子信号传导。在记录区域（齿状颗粒细胞层）局部灌注0.1毫摩尔ZnAF-2DA会影响体内齿状回长时程增强（LTP），但灌注细胞外锌离子螯合剂1-10毫摩尔CaEDTA则不会，这表明齿状颗粒细胞中细胞内锌离子信号传导的阻断会影响齿状回LTP。本研究表明，齿状回中的细胞内锌离子信号传导可能通过齿状回LTP表达对物体识别记忆是必需的。
