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



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



Molecular and Cellular Biology 26(8): 2936-2946



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.

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Accession: 049652578

Download citation: RISBibTeXText

PMID: 16581769

DOI: 10.1128/MCB.26.8.2936-2946.2006


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