title: Identification and Characterization of the V(D)J Recombination Activating Gene 1 in Long-Term Memory of Context Fear Conditioning.
abstract: An increasing body of evidence suggests that mechanisms related to the introduction and repair of DNA double strand breaks (DSBs) may be associated with long-term memory (LTM) processes. Previous studies from our group suggested that factors known to function in DNA recombination/repair machineries, such as DNA ligases, polymerases, and DNA endonucleases, play a role in LTM. Here we report data using C57BL/6 mice showing that the V(D)J recombination-activating gene 1 (RAG1), which encodes a factor that introduces DSBs in immunoglobulin and T-cell receptor genes, is induced in the amygdala, but not in the hippocampus, after context fear conditioning. Amygdalar induction of RAG1 mRNA, measured by real-time PCR, was not observed in context-only or shock-only controls, suggesting that the context fear conditioning response is related to associative learning processes. Furthermore, double immunofluorescence studies demonstrated the neuronal localization of RAG1 protein in amygdalar sections prepared after perfusion and fixation. In functional studies, intra-amygdalar injections of RAG1 gapmer antisense oligonucleotides, given 1 h prior to conditioning, resulted in amygdalar knockdown of RAG1 mRNA and a significant impairment in LTM, tested 24 h after training. Overall, these findings suggest that the V(D)J recombination-activating gene 1, RAG1, may play a role in LTM consolidation.
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA; Functional Genomics Research Center, Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Edgardo
authors: E
authors: Castro-Pérez
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Emilio
authors: E
authors: Soto-Soto
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Marizabeth
authors: M
authors: Pérez-Carambot
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Dawling
authors: D
authors: Dionisio-Santos
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Kristian
authors: K
authors: Saied-Santiago
authors: Department of Computer Science, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA; High Performance Computing Facility, Central Administration, San Juan, PR 00931, USA.
authors: Humberto G
authors: HG
authors: Ortiz-Zuazaga
authors: Molecular and Cellular Cognition Laboratory, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA; Functional Genomics Research Center, Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3360, USA.
authors: Sandra
authors: S
authors: Peña de Ortiz
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D016654:Genes, RAG-1; D006624:Hippocampus / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein