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The Journal of Neuroscience, April 21, 2004, 24(16):3933-3943; doi:10.1523/JNEUROSCI.5646-03.2004

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Development/Plasticity/Repair
A Bioinformatics Analysis of Memory Consolidation Reveals Involvement of the Transcription Factor c-Rel

Jonathan M. Levenson,1 Sangdun Choi,4 Sun-Young Lee,4 Yun Anna Cao,4 Hyung Jin Ahn,2 Kim C. Worley,3 Marina Pizzi,5 Hsiou-Chi Liou,6 and J. David Sweatt1

1Division of Neuroscience, 2Department of Molecular Physiology and Biophysics, and 3Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, 4Division of Biology, California Institute of Technology, Pasadena, California 91125, 5Division of Pharmacology and Experimental Therapeutics, Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, 25123 Brescia, Italy, and 6Department of Microbiology and Immunity, Weill Medical College of Cornell University, New York, New York 10021

Consolidation of long-term memory (LTM) is a complex process requiring synthesis of new mRNAs and proteins. Many studies have characterized the requirement for de novo mRNA and protein synthesis; however, few studies have comprehensively identified genes regulated during LTM consolidation. We show that consolidation of long-term contextual memory in the hippocampus triggers altered expression of numerous genes encompassing many aspects of neuronal function. Like contextual memory formation, this altered gene expression required NMDA receptor activation and was specific for situations in which the animal formed an association between a physical context and a sensory stimulus. Using a bioinformatics approach, we found that regulatory elements for several transcription factors are over-represented in the upstream region of genes regulated during consolidation of LTM. Using a knock-out mouse, we found that c-rel, one of the transcription factors identified in our bioinformatics study, is necessary for hippocampus-dependent long-term memory formation.

Key words: memory; hippocampus; microarray; bioinformatics; NF{kappa}B; transcription factor

Received Dec 22, 2003; revised February 5, 2004; accepted March 3, 2004.




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