a, Genome-wide RNA-seq was performed on the dorsal hippocampus of eGFP control and shACSS2-knockdown mice. The analysis was focused on the set of previously identified and validated genes that become upregulated during the sensitive period following memory retrieval. The baseline expression of immediate early genes in untrained animals was not changed in shACSS2-AAV9 mice when compared to eGFP-AAV9 control mice (CC, circadian control). b, During the sensitive period following contextual memory retrieval (RT, 30 min post-exposure to conditioning chamber 24 h after fear conditioning), immediate early genes were upregulated in the dorsal hippocampus of control injected mice. By contrast, the dynamic retrieval-induced expression of these early response genes is absent in ACSS2-knockdown mice (P = 0.001, paired t-test). c, Induction defect of immediate early genes in shACSS2-AAV9 injected animals (RT/CC). d, The baseline expression of genes that were downregulated after contextual memory retrieval is not altered in ACSS2-knockdown mice. e, Downregulation of retrieval-responsive genes occurs in both eGFP control and ACSS2-knockdown mice, except for Cldn5. f, Retrieval-induced downregulation of retrieval-responsive genes in the dorsal hippocampus in eGFP control versus shACSS2-knockdown mice (RT/CC).