Influx of extracellular Zn2+ into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation
Influx of extracellular Zn2+ into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation
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DOI：
10.1016/j.neuroscience.2015.07.042
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发表时间：
2015-09
期刊：
影响因子：
3.3
通讯作者：
A. Takeda;M. Suzuki;M. Tempaku;K. Ohashi;H. Tamano
中科院分区：
文献类型：
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作者：
A. Takeda;M. Suzuki;M. Tempaku;K. Ohashi;H. Tamano
用微透析探针连接记录电极，并经微透析探针灌注人工脑脊液（ACSF），在大鼠海马CA 1区（CA 1区）诱发长时程增强（LTP），用CaEDTA和ZnAF-2DA（细胞外和细胞内锌离子螯合剂）灌流，在大鼠海马CA 1区（CA 1区）诱发LTP，并观察其生理意义。提示细胞外Zn ~（2+）的内流是体内CA_1 LTP诱导所必需的。在将ZnAF-2DA局部注射到CA 1中后1小时，CA 1中细胞内Zn 2+的增加与细胞内ZnAF-2螯合，表明当在ZnAF-2DA注射后1小时进行学习时，在学习期间诱导的细胞内Zn 2+信号传导被细胞内ZnAF-2阻断。ZnAF-2DA注射后1 h进行物体识别测试训练时，物体识别受到影响。这些数据表明，在CA 1的细胞内Zn 2+信号是需要通过LTP的对象识别记忆。令人惊讶的是，在0.1-1 μM ZnCl 2灌注下，体内CA 1 LTP受到影响，而不像以前的数据，在1-5 μM ZnCl 2存在下，体外CA 1 LTP增强。细胞外Zn ~（2+）内流到CA_1锥体细胞在CA_1 LTP中具有双向作用。目前的研究表明，细胞外Zn 2+流入CA 1神经元的程度是至关重要的LTP和认知性能。
Physiological significance of synaptic Zn2+signaling was examined in the CA1 of young rats.In vivoCA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe.In vivoCA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn2+chelators, respectively, suggesting that the influx of extracellular Zn2+is required forin vivoCA1 LTP induction. The increase in intracellular Zn2+was chelated with intracellular ZnAF-2 in the CA1 1 h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn2+signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1 h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1 h after ZnAF-2DA injection. These data suggest that intracellular Zn2+signaling in the CA1 is required for object recognition memory via LTP. Surprisingly,in vivoCA1 LTP was affected under perfusion with 0.1–1 μM ZnCl2, unlike the previous data thatin vitroCA1 LTP was enhanced in the presence of 1–5 μM ZnCl2. The influx of extracellular Zn2+into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn2+influx into CA1 neurons is critical for LTP and cognitive performance.