Abstract
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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Activins / genetics
-
Activins / metabolism
-
Analysis of Variance
-
Animals
-
Animals, Genetically Modified
-
CREB-Binding Protein / genetics
-
CREB-Binding Protein / metabolism*
-
Carrier Proteins / genetics
-
Carrier Proteins / metabolism
-
Cells, Cultured
-
Central Nervous System / cytology
-
Conditioning, Psychological / drug effects*
-
Conditioning, Psychological / physiology
-
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
-
RNA-Binding Proteins / genetics
-
RNA-Binding Proteins / metabolism
-
Receptors, N-Methyl-D-Aspartate / genetics
-
Receptors, N-Methyl-D-Aspartate / metabolism*
Substances
-
Carrier Proteins
-
Drosophila Proteins
-
Excitatory Amino Acid Agonists
-
Homer Scaffolding Proteins
-
NR1 NMDA receptor
-
Nicotinic Agonists
-
RNA-Binding Proteins
-
Receptors, N-Methyl-D-Aspartate
-
homer protein, Drosophila
-
Activins
-
stau protein, Drosophila
-
N-Methylaspartate
-
Nicotine
-
CREB-Binding Protein
-
Mitogen-Activated Protein Kinase Kinases
-
Magnesium