Mg(2+) block of Drosophila NMDA receptors is required for long-term memory formation and CREB-dependent gene expression.
NMDA receptor (NMDAR) channels allow Ca(2+) influx only during correlated activation of both pre- and postsynaptic cells; a Mg(2+) 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 Mg(2+) block in these processes remains unclear. Using transgenic flies expressing NMDARs defective for Mg(2+) block, we found that Mg(2+) 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 Mg(2+) block defective NMDARs. Furthermore, we show that genetic and pharmacological reduction of Mg(2+) block significantly increases expression of a CREB repressor isoform. Our results suggest that Mg(2+) block of NMDARs functions to suppress basal expression of a CREB repressor, thus permitting CREB-dependent gene expression upon LTM induction.
Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
Tomoyuki
T
Miyashita
Yoshiaki
Y
Oda
Junjiro
J
Horiuchi
Jerry C P
JC
Yin
Takako
T
Morimoto
Minoru
M
Saitoe
D028341:Activins / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008274:Magnesium / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011679:Pupa; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D018690:Excitatory Amino Acid Agonists; D000072233:Homer Scaffolding Proteins; C409466:NR1 NMDA receptor; D018722:Nicotinic Agonists; D016601:RNA-Binding Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C000606630:homer protein, Drosophila; D028341:Activins; C069927:stau protein, Drosophila; D016202:N-Methylaspartate; D009538:Nicotine; D050882:CREB-Binding Protein; D020929:Mitogen-Activated Protein Kinase Kinases; D008274:Magnesium