c Title Loaded From File Synchrotronbased TIR analysis with the retrosplenial cortex RSC and corpus callosum CC of WT and PS cKOTau mice at 6 months of age. Insets magnified images indicated by squares displaying prominent NFL somatic staining in hippocampal neurons of PS cKOTau mice. Scale bar one hundred m. b Left Biochemical analysis of hippocampal lysates applying SMI312 NFMH and NFL antibodies. Correct Quantification of NFH 200 kDa, NFM 150 kDa, SMIlabeled 600 kDa and NFL 70 kDa bands in independent membranes. Protein levels were normalized to GAPDH. Values represent mean s.e.m. n 4 micegroup. Statistical evaluation was determined by twoway ANOVA followed by Tukeys post hoc tests. P 0.001. c Synchrotronbased TIR analysis with the retrosplenial cortex RSC and corpus callosum CC of WT and PS cKOTau mice at six months of age. Second derivative absorbances d2A of sheethelix d2A1635d2A1656, and intermolecularAmide I d2A1625d2A16351656 and antiparallelAmide I d2A1695 d2A16351656 protein structures. Values represent the minimum, the maximum as well as the median with the average of 100 spectramouse n four micegroup. Statistical analysis was determined by oneway ANOVA followed by Sidaks post hoc tests. P 0.05, P 0.001, P 0.0001. d Representative infrared heat maps of intermolecularAmide I left photos scale bar 50 m and consecutive immunohistological sections of aggregated tau detected by MC1 staining middle images and Congo red staining right pictures scale bar 25 m within the RSC and CC of WT and PS cKOTau mice.SotoFagu et al. acta neuropathol commun2021 9Page 13 ofFig. 8 See legend on earlier web page.SotoFagu et al. acta neuropathol commun2021 9Page 14 ofFig. 9 Loss of PS function causes hippocampaldependent memory deficits in Tau transgenic mice. Morris water maze and CFC was performed with six monthold WT, Tau, PS1 cKOTau and PS cKOTau mice. a Visible platform phase consisted in six trials and platform latency in seconds was measured. b For the duration of studying phase, which consisted in six trials in the course of five consecutive days, latency towards the platform in seconds was measured. c Latency towards the first entry to the target quadrant in seconds, number of crossings for the target quadrant and percentage of time in the target quadrant in the very first 30 s in the test had been analyzed. d Representative heat map of every analyzed group through the probe test. e CFC showing the percentage of freezing time straight away and 24 h immediately after conditioning. Values represent mean freezing time s.e.m. n 70 micegroup. Statistical analysis was determined by one particular or twoway ANOVA followed by Tukeys post hoc tests. P 0.05, P 0.01, P 0.001, P 0.PS cKOTau mice spent substantial longer latencies than Tau and PS1 cKOTau mice Twoway ANOVA P 0.0001. Within the probe trial on day six, PS cKOTau mice spent far more time to uncover the target quadrant, and crossed less often and spent much less time inside the target quadrant than the rest of groups oneway ANOVA latency, crossing and occupancy in target quadrant, P 0.05 Fig.9,cd. In contextual worry conditioning,freezing responses quickly just after shock had been related in all experimental groups, suggesting no differences in sensing the footshock Fig.