Extended Data Figure 8: Attenuation of ACSS2 expression in the dorsal hippocampus impairs object location memory. | Nature

Extended Data Figure 8: Attenuation of ACSS2 expression in the dorsal hippocampus impairs object location memory.

From: Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory

Extended Data Figure 8

a, ACSS2 RNA in situ hybridization on ACSS2 in sagittal section of hippocampal region CA1 (left, reference atlas adapted from Allen Mouse Brain Atlas12; right, in situ hybridization; HPC, hippocampus proper). b, Weight of eGFP-AAV9 control and shACSS2-AAV9 knockdown mice before intracranial surgery, and following recovery before object location memory (OLM) training (NS, n = 10 per group, error bars show s.d.). c, d, ACSS2 knockdown mice showed no defect in locomotion or thigmotaxis (tendency to remain close to vertical surfaces in an open field, a measure of anxiety), as quantified over 5 min in the open field test; c shows example heat map of tracking data (NS, n = 10 per group, error bars show s.d.). e, Exploration times by eGFP-AAV9 control and shACSS2-AAV9 knockdown mice recorded for the three objects (O1–3) during the first OLM training session (TR) and the 24-h retention test (NL, object in novel location; FL, objects in former location). f, Compared to the control eGFP-AVV9 mice, ACSS2-knockdown mice showed no defect in contextual fear memory. Freezing in chamber on day of contextual fear conditioning was recorded and quantified pre-shock (FC Training; NS, n = 10 per cohort, error bars show s.d.). Fear memory was measured as the freezing response after re-exposure to the context 1 day after contextual fear conditioning (aversive stimulus: 1.5 mA electrical shock; NS, n = 10 per cohort, error bars show s.d.). g, RNA-seq was performed on the dorsal hippocampus of eGFP control and shACSS2-knockdown animals. Global transcript levels were not affected by ACSS2 knockdown (dHPC, dorsal hippocampus; four animals per group, two replicates for each condition; NS, paired t-test, error bars show s.d.). h, Baseline expression of immediate-early genes in untrained animals was unaltered in ACSS2-knockdown mice. RNA-seq was performed on the dorsal hippocampus of eGFP control and shACSS2-knockdown mice (r = 0.82, P < 0.0001; HCC, homecage circadian control).

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