Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Mol Neurobiol. 2018 Feb;55(2):1498-1508. doi: 10.1007/s12035-017-0428-3. Epub 2017 Feb 7.
The idea that maintained LTP and memory are lost by either increase in intracellular Zn in dentate granule cells or increase in intracellular Ca 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 Zn but not high K-induced increase in intracellular Ca. High K-induced disturbances of LTP and intracellular Zn 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 Zn, but not increase in intracellular Ca. NMDA and glucocorticoid, which induced Zn release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca influx.
研究了通过增加齿状回颗粒细胞内的锌或增加细胞内的钙来维持 LTP 和记忆的想法，以阐明过量突触兴奋诱导的增加的意义。将高 K 注入齿状回会损害维持的 LTP 和空间记忆，但通过共注射 CaEDTA 可以挽救，CaEDTA 可以阻断高 K 诱导的细胞内锌增加，但不阻断高 K 诱导的细胞内钙增加。用 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂 6-氰基-7-硝基喹喔啉-2,3-二酮共注射可以挽救高 K 诱导的 LTP 和细胞内锌紊乱，但不能挽救 NMDA 受体、代谢型谷氨酸受体和电压依赖性钙通道的阻断剂共注射的挽救作用。此外，AMPA 损害维持的 LTP，而共注射 CaEDTA 可以挽救这种损害，CaEDTA 可以阻断细胞内锌的增加，但不能阻断细胞内钙的增加。诱导锌从内部储存中释放的 NMDA 和糖皮质激素不会损害维持的 LTP。本研究表明，通过 AMPA 受体进入齿状回颗粒细胞的锌内流会丧失维持的 LTP 和记忆。调节锌流入齿状回颗粒细胞不仅对记忆获取而且对记忆保留比对钙流入更关键。
