title: Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory.
abstract: Whether the consolidation and reconsolidation long-term memory relies on qualitatively different molecular and cellular processes is controversial. Using a novel experimental strategy of combining intrahippocampal antisense oligodeoxynucleotides targeting BDNF or zif268 to the block consolidation or reconsolidation of contextual fear memory respectively, and Affymetrix microarray technology, we identified a comprehensive list of nonoverlapping candidate genes regulated in CA1 during the initial stages consolidation and reconsolidation. Using RT-qPCR in subsequent validation experiments, we estimated that over 80% of the candidates reflect gene transcripts truly regulated following the acquisition or retrieval of contextual fear memory. Statistical and over-representation bioinformatics analyses revealed that cellular processes and signaling mechanisms were differentially regulated during consolidation and reconsolidation, particularly those associated with pro-inflammatory cytokine signaling. This predicts that the two mnemonic processes are qualitatively as well as quantitatively distinct. This experimental strategy was further validated because the cytokine interleukin 1 (IL-1) was reciprocally regulated in CA1 after contextual fear conditioning and fear memory retrieval, and we showed for the first time that that IL-1 receptor mediated signaling in the hippocampus was necessary for reconsolidation.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Barnes
authors.forename: Anne
authors.initials: A
authors.lastname: Kirtley
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: Thomas
mesh_terms: D000818:Animals; D005239:Fear / Q000502:physiology; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1