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Molecular and Cellular Biology, April 2006, p. 2936-2946, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.2936-2946.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

NF-B Regulates Spatial Memory Formation and Synaptic Plasticity through Protein Kinase A/CREB Signaling

Barbara Kaltschmidt,¹ Delphine Ndiaye,² Martin Korte,^3, Stéphanie Pothion,⁴ Laurence Arbibe,^2, Maria Prüllage,¹ Julia Pfeiffer,¹ Antje Lindecke,¹ Volker Staiger,³ Alain Israël,² Christian Kaltschmidt,^1* and Sylvie Mémet^2*

Institut für Neurobiochemie, Universität Witten/Herdecke, Stockumer Strasse 10, D-58448 Witten, Germany,¹ Unité de Biologie Moléculaire de l'Expression Génique, URA CNRS 2582, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France,² Max-Planck-Institut für Neurobiologie, Department of Cellular and Systems Neurobiology, Am Klopferspitz 18a, D-82152 Martinsried, Germany,³ Key-Obs SA, Centre d'Innovation, 16 rue Léonard de Vinci, 45074 Orléans Cedex 2, France⁴

Received 30 June 2005/ Returned for modification 12 September 2005/ Accepted 27 January 2006

Synaptic activity-dependent de novo gene transcription is crucial for long-lasting neuronal plasticity and long-term memory. In a forebrain neuronal conditional NF-B-deficient mouse model, we demonstrate here that the transcription factor NF-B regulates spatial memory formation, synaptic transmission, and plasticity. Gene profiling experiments and analysis of regulatory regions identified the catalytic subunit of protein kinase A (PKA), an essential memory regulator, as a new NF-B target gene. Consequently, NF-B inhibition led to a decrease in forskolin-induced CREB phosphorylation. Collectively, these results disclose a novel hierarchical transcriptional network involving NF-B, PKA, and CREB that leads to concerted nuclear transduction of synaptic signals in neurons, accounting for the critical function of NF-B in learning and memory.

Present address: Zoological Institute, TU Braunschweig, D-38106 Braunschweig, Germany.

Present address: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 389, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.

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