Extended Data Figure 9.

ACSS2 regulates retrieval-induced upregulation immediate-early genes in vivo. (a) Genome-wide RNA-seq was performed on the dorsal hippocampus of eGFP control and shACSS2 knockdown animals. 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 is 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 24h following fear conditioning), immediate-early genes are upregulated in dorsal HPC in the control injected animals. In contrast, the dynamic retrieval-induced expression of these early response genes is absent in ACSS2 knockdown animals (p = 0.001, Paired T test). (c) Boxplot shows the induction defect of immediate-early genes in shACSS2-AAV9 injected animals (RT/CC). (d) The baseline expression of genes that are downregulated following contextual memory retrieval is not altered in ACSS2 knockdown animals. (e) Downregulation of retrieval-responsive genes occurs both in eGFP control and ACSS2 knockdown mice, except Cldn5. (f) Boxplot compares retrieval-induced downregulation of retrieval-responsive genes in the dorsal hippocampus in eGFP control versus shACSS2 knockdown (RT/CC).