Fig. 3: Activation of the dHP and inhibition of the VMT rescues the expression of high load incidental LTM.

a Schematic of the experimental design showing the timing of injection of an activatory DREADDs in the dHP or an inhibitory one in the VMT of female mice and the experimental course. b AAV-CaMKIIa-HA-rM3D(Gs)-IRES-mCitrine was injected in the dHP of females. Bar chart represents increased new object % exploration for CNO-treated females compared to controls. b′ Bar charts represent western blot analysis of p-S845/GluR1 levels in the dHP of vehicle and CNO-treated mice, which is increased by dHP chemogenetic activation. No change was detected in the expression of GluR1. On the right are shown representative bands for each condition. b″ Representative images of AAV expression in the dHP; scale bar 100 µm. c AAV-CaMKIIa-HA-rM4D(Gi)-IRES-mCitrine was injected in the VMT of female mice. Bar charts represent increased new object % exploration in CNO-treated females compared to controls. c′ Bar charts represent western blot analysis of p-S845/GluR1 levels in the hippocampus of vehicle and CNO-treated mice, which shows a significant increase after VMT inhibition. Concomitant we found that VMT inhibition also increased the GluR1 levels. On the right are shown representative bands for each condition. c″ Representative images of AAV expression in the VMT; scale bar 100 µm. d Schematic of the experimental design showing the timing of injection of an activatory DREADDs in the VMT of male mice and the experimental course. d′ AAV-CaMKIIa-HA-rM3D(Gs)-IRES-mCitrine was injected in the VMT of males. Bar charts on the left represent new object % exploration for vehicle and CNO-treated mice showing that VMT activation induced a memory consolidation capacity limit in males. Bar charts on the right represent western blot analysis of p-S845 and GluR1 levels in the dHP of vehicle and CNO-treated mice, which were both decreased by the chemogenetic activation of the VMT, while no change was detected on their ratio. Representative bands for each condition are shown on the right. *p < 0.05 between groups. Data in bar charts are presented as mean values ± SEM. Dashed lines in (b′) and (c′) delineate cut parts from the same western blot. For statistics see Supplementary Table 5.