Mg²⁺ Block of Drosophila NMDA Receptors Is Required for Long-Term Memory Formation and CREB-Dependent Gene Expression

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• 作者：Tomoyuki Miyashita¹ ; Yoshiaki Oda² ; Junjiro Horiuchi³ ; Jerry  ; C.P. Yin⁴ ; Takako Morimoto² ; Minoru Saitoe¹ ; ^{saito-mn@igakuken.or.jp}
• 刊名：Neuron
• 出版年：2012
• 期刊代码：45_08966273
• 类别：neu
• 出版时间：7 June, 2012
• 卷：74
• 期：5
• 页码：887-898
• 文件大小：874 K

摘要

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Summary

NMDA receptor (NMDAR) channels allow Ca²⁺ influx only during correlated activation of both pre- and postsynaptic cells; a Mg²⁺ block mechanism suppresses NMDAR activity when the postsynaptic cell is inactive. Although the importance of NMDARs in associative learning and long-term memory (LTM) formation has been demonstrated, the role of Mg²⁺ block in these processes remains unclear. Using transgenic flies expressing NMDARs defective for Mg²⁺ block, we found that Mg²⁺ block mutants are defective for LTM formation but not associative learning. We demonstrate that LTM-dependent increases in expression of synaptic genes, including homer, staufen, and activin, are abolished in flies expressing Mg²⁺ block defective NMDARs. Furthermore, we show that genetic and pharmacological reduction of Mg²⁺ block significantly increases expression of a CREB repressor isoform. Our results suggest that Mg²⁺ block of NMDARs functions to suppress basal expression of a CREB repressor, thus permitting CREB-dependent gene expression upon LTM induction.