Fig. 2: Females show an apparent capacity limit after memory consolidation, associated with VMT hyperactivation and dHP hypoactivation compared to males.

a Bar charts report new object % exploration in the 6-IOT/DOT for STM (1 min) and LTM (24 h) of male (6-IOT: 1 min n = 15, 24 h n = 8; 6-DOT: 1 min n = 14, 24 h n = 19) and female (6-IOT: 1 min n = 15, 24 h n = 8; 6-DOT: 1 min n = 14, 24 h n = 20) mice. The performance of females in the 6-DOT at 24 h delay was significantly lower than that in the 6-IOT and that of males in the 6-DOT. b Schematic of the c-Fos mapping experiment. c Bar charts represent the mean of c-Fos⁺ cells normalized on naive per sex for each brain region analyzed. The VMT was the brain region found significantly activated only in females exposed to the 6-DOT. The CA1-CA3 of the dHP was found significantly activated only in male mice exposed to the 6-DOT. The bottom panels show representative photographs of the dHP and the VMT in each experimental condition. Scale bar 50 µm. c′ The Spearman correlation coefficient between VMT and dHP c-Fos⁺ cells was positive and significant for both sexes. c″ Illustration of the opposite pattern of activation between the dHP and the VMT in the two sexes. d, e Load-dependent activation of c-Fos in the VMT and the dHP for both sexes. The VMT was significantly more active in female mice after the 6-DOT compared to lower load conditions (6-IOT and 3-DOT) and to males (d). The same happens to the dHP of males (e). Data are normalized on naive c-Fos expression. *p < 0.05 naive vs test (within sexes), ^#p < 0.05 test between sexes (Bonferroni correction). Data in bar charts are presented as mean values ± SEM. For statistics see Supplementary Table 5 and Supplementary Fig. 2. PL = prelimbic cortex; IL = infralimbic cortex; ACC = anterior cingulate cortex; VMT = ventral midline thalamus (including the reuniens and the rhomboid thalamic nuclei); ENT = entorhinal cortex; PER = perirhinal cortex; dHP = dorsal hippocampus; DG = dentate gyrus; vHP = ventral hippocampus.