Fig. 1

oTau impairs CREB phosphorylation during memory formation. a SDS-PAGE gel of recombinant oTau 4R/2 N preparation shows the presence of monomers and different size oligomers. b-c Phospho-CREB immunoblots of hippocampal homogenates from mice previously treated with/without a foot-shock to induce fear memory. Hippocampi were harvested 1 min (b) and 60 min (c) after the foot-shock or sham exposure in the fear-conditioning chamber. Graphs showing the average ratio of phospho-CREB (p-CREB)/total-CREB (t-CREB) (t-test at 1 min: p = 0.007; at 60 min: p = 0.03; n = 4 per each group, 2 males and females for each experimental condition; Bas = Baseline; FS = Footshock). d-e acH3K27, c-Fos and Arc immunoblots of hippocampal homogenates from mice under the same conditions as B-C. Graphs showing the average ratio of acH3K27/total-H3 (t-H3) (at 1 min: p = 0.08; at 60 min: p = 0.002), c-Fos (at 1 min: p = 0.05; at 60 min: p = 0.02), and Arc (at 1 min: p = 0.001; at 60 min: p = 0.004); n = 4 animals, 2 males and females for each experimental condition). f-g Phospho-CREB immunoblots of hippocampal homogenates from mice treated with vehicle (Veh) or oTau (22.95 μg/ml). Hippocampi were harvested 1 min (f) and 60 min (g) after the foot-shock. Graphs showing the average ratio of p-CREB/t-CREB (unpaired t-test at 1 min: p = 0.016; at 60 min: p = 0.044; n = 4 per each group, 2 males and females for each experimental condition). h-i acH3K27, c-Fos and Arc immunoblots of hippocampal homogenates from mice treated with vehicle (Veh) or oTau (22.95 μg/ml) under the same conditions as f-g. Graphs showing the average ratio of acH3K27/t-H3 (at 1 min: p = 0.014; at 60 min: p = 0.012), c-Fos (at 1 min: p < 0.0001; at 60 min: p = 0.013), and Arc (at 1 min: p = 0.025; at 60 min: p = 0.026). n = 4 animals, 2 males and females for each experimental condition. *p < 0.05, **p < 0.01; ***p < 0.005; ****p < 0.0001