Fig. 6

Chemogenetic modulation of hippocampus-dependent memory in 5-month-old orx-Cre/A53T mice. Schematic diagram of AAV vector encoding DREADD-mCherry driven by the human synapsin promoter (hSyn) promoter sequence and flanked by dual flox sites for recombination in the presence of Cre-recombinase (a). Cre expression in orx-Cre mice is driven by the prepro-orexin-promoter. Schematic representation of DREADD virus injection site within the lateral hypothalamus (LH) (b). DREADD-virus constructs were injected bilaterally (333 nl/5 min). No statistically significant differences were observed in the total number of entries between experimental groups (c). No statistically significant differences were observed in total exploration time between experimental groups (d). No statistically significant differences were observed in novel object exploration time between experimental groups (e). No statistically significant differences were observed in familiar object exploration time between experimental groups (f). Reduced discrimination in cDREADD orx-Cre/A53T mice was observed compared to cDREADD orx-Cre mice (g). Compared to orx-Cre qDREADD mice, both orx-Cre/A53T cDREADD and orx-Cre/A53T qDREADD showed reductions in discrimination ratio. CNO intervention increased discrimination ratio in orx-Cre/A53T qDREADD mice (g) compared to orx-Cre/A53T cDREADD mice. (n = 10/group; one-way ANOVA, Tukey’s; *p < 0.05, ***p < 0.005)