The Journal of Neuroscience, May 6, 2009, 29(18):5726-5737; doi:10.1523/JNEUROSCI.4033-08.2009
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Cellular/Molecular
Identification of Flap Structure-Specific Endonuclease 1 as a Factor Involved in Long-Term Memory Formation of Aversive Learning
Lorena Saavedra-Rodríguez,1,2
Adrinel Vázquez,1,2
Humberto G. Ortiz-Zuazaga,4
Nataliya E. Chorna,3
Fernando A. González,3
Lissette Andrés,1
Karen Rodríguez,1
Fernando Ramírez,1
Alan Rodríguez,1 and
Sandra Peña de Ortiz1,2
1Molecular and Cellular Cognition Laboratory and 2Functional Genomics Research Center, Department of Biology, and 3Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico 00931-3360, and 4High Performance Computing Facility, University of Puerto Rico, Central Administration, San Juan, Puerto Rico 00931
Correspondence should be addressed to Dr. Sandra Peña de Ortiz, Department of Biology, University of Puerto Rico, P.O. Box 23360, San Juan, PR 00931-3360. Email: sandra{at}hpcf.upr.edu
We previously proposed that DNA recombination/repair processes play a role in memory formation. Here, we examined the possible role of the fen-1 gene, encoding a flap structure-specific endonuclease, in memory consolidation of conditioned taste aversion (CTA). Quantitative real-time PCR showed that amygdalar fen-1 mRNA induction was associated to the central processing of the illness experience related to CTA and to CTA itself, but not to the central processing resulting from the presentation of a novel flavor. CTA also increased expression of the Fen-1 protein in the amygdala, but not the insular cortex. In addition, double immunofluorescence analyses showed that amygdalar Fen-1 expression is mostly localized within neurons. Importantly, functional studies demonstrated that amygdalar antisense knockdown of fen-1 expression impaired consolidation, but not short-term memory, of CTA. Overall, these studies define the fen-1 endonuclease as a new DNA recombination/repair factor involved in the formation of long-term memories.
Received Aug. 24, 2008;
revised March 11, 2009;
accepted March 24, 2009.
Correspondence should be addressed to Dr. Sandra Peña de Ortiz, Department of Biology, University of Puerto Rico, P.O. Box 23360, San Juan, PR 00931-3360. Email: sandra{at}hpcf.upr.edu
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