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

• Published in: Neuron (Cambridge, Mass.) Vol. 74; no. 5; pp. 887 - 898
• Main Authors: Miyashita, Tomoyuki, Oda, Yoshiaki, Horiuchi, Junjiro, Yin, Jerry C.P., Morimoto, Takako, Saitoe, Minoru
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Inc 07.06.2012; Elsevier Limited
• Subjects: Activin; Associative learning; Calcium channels; Calcium influx; Cyclic AMP response element-binding protein; Drosophila; Gene expression; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Insects; Long term memory; Magnesium; Mutation; N-Methyl-D-aspartic acid receptors; Neurons; Odors; Repressors; Studies
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2012.03.039

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. ► Mg2+ block mutant flies are defective for long-term olfactory aversive memory ► Mg2+ block is required for training-induced expression of long-term memory genes ► A CREB repressor isoform abolishes induction of long-term memory genes ► Mg2+ block functions to inhibit basal expression of CREB repressor Mg2+ block allows NMDA receptors to function as “Hebbian coincidence detectors,” yet the molecular and behavioral importance of Mg2+ block is unclear. Miyashita et al. show that Drosophila mutants with disrupted Mg2+ block show disrupted long-term memory resulting from increased expression of a CREB repressor.