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.