NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A/CREB signaling

Synaptic activity-dependent de novo gene transcription is crucial for long-lasting neuronal plasticity and long-term memory. In a forebrain neuronal conditional NF-kappaB-deficient mouse model, we demonstrate here that the transcription factor NF-kappaB regulates spatial memory formation, synaptic t...

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Bibliographic Details
Published in:Molecular and cellular biology 2006-04, Vol.26 (8), p.2936-2946
Main Authors: Kaltschmidt, Barbara, Ndiaye, Delphine, Korte, Martin, Pothion, Stéphanie, Arbibe, Laurence, Prüllage, Maria, Pfeiffer, Julia, Lindecke, Antje, Staiger, Volker, Israël, Alain, Kaltschmidt, Christian, Mémet, Sylvie
Format: Article
Language:English
Subjects:
Animals
Biochemistry, Molecular Biology
Cells, Cultured
Colforsin - pharmacology
Cyclic AMP Response Element-Binding Protein
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinases - metabolism
Electrophoretic Mobility Shift Assay
Electrophysiology
Forskolin
Gene Expression Profiling
Hippocampus
Hippocampus - cytology
Hippocampus - physiology
Immunohistochemistry
Life Sciences
Male
Memory
Memory - physiology
Mice
Mice, Transgenic
NF-kappa B - physiology
Phosphorylation - drug effects
Synaptic Transmission - physiology
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Summary:Synaptic activity-dependent de novo gene transcription is crucial for long-lasting neuronal plasticity and long-term memory. In a forebrain neuronal conditional NF-kappaB-deficient mouse model, we demonstrate here that the transcription factor NF-kappaB regulates spatial memory formation, synaptic transmission, and plasticity. Gene profiling experiments and analysis of regulatory regions identified the alpha catalytic subunit of protein kinase A (PKA), an essential memory regulator, as a new NF-kappaB target gene. Consequently, NF-kappaB inhibition led to a decrease in forskolin-induced CREB phosphorylation. Collectively, these results disclose a novel hierarchical transcriptional network involving NF-kappaB, PKA, and CREB that leads to concerted nuclear transduction of synaptic signals in neurons, accounting for the critical function of NF-kappaB in learning and memory.
ISSN:0270-7306
1098-5549
DOI:10.1128/mcb.26.8.2936-2946.2006