Mg(2+) block of Drosophila NMDA receptors is required for long-term memory formation and CREB-dependent gene expression

• Published in: Neuron (Cambridge, Mass.) Mass.), 2012-06, Vol.74 (5), p.887
• Main Authors: Miyashita, Tomoyuki, Oda, Yoshiaki, Horiuchi, Junjiro, Yin, Jerry C P, Morimoto, Takako, Saitoe, Minoru
• Format: Article
• Language: English
• Subjects: Activins - genetics; Activins - metabolism; Analysis of Variance; Animals; Animals, Genetically Modified; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cells, Cultured; Central Nervous System - cytology; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; CREB-Binding Protein - genetics; CREB-Binding Protein - metabolism; Dose-Response Relationship, Drug; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Electric Stimulation; Excitatory Amino Acid Agonists - pharmacology; Homer Scaffolding Proteins; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Magnesium - pharmacology; Mitogen-Activated Protein Kinase Kinases - genetics; Mitogen-Activated Protein Kinase Kinases - metabolism; Mutagenesis - physiology; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - physiology; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Odorants; Olfactory Pathways - drug effects; Olfactory Pathways - physiology; Patch-Clamp Techniques; Pupa; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism
• ISSN: 1097-4199
• DOI: 10.1016/j.neuron.2012.03.039

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.