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 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.
Kaltschmidt
Barbara
B
Universität Witten/Herdecke, Institut für Neurobiochemie, Stockumer Strasse 10, D-58448 Witten, Germany. c.kaltschmidt@uni-wh.de
Ndiaye
Delphine
D
Korte
Martin
M
Pothion
Stéphanie
S
Arbibe
Laurence
L
Prüllage
Maria
M
Pfeiffer
Julia
J
Lindecke
Antje
A
Staiger
Volker
V
Israël
Alain
A
Kaltschmidt
Christian
C
Mémet
Sylvie
S
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004594:Electrophysiology; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases