Fig. 5
Overexpression of Per1 in the dorsal hippocampus ameliorates age-related impairments in object location memory. a Schematic of lentivirus construct used to overexpress v5-tagged Per1 (pLVX-v5Per1) compared to the empty vector control (pLVX-EV). b Per1 mRNA was significantly increased 24 and 48 h after transfection of pLVX-v5Per1 in HT22 cells compared to cells transfected with EV (Two-way ANOVA: Group x Timepoint interaction (F(1,8) = 52.8, p < 0.001), Sidak’s post hoc tests, ***p < 0.001, n = 3, 3, 3, 3). c 18-m.o. mice given hippocampal infusions of pLVX-v5Per1 showed significantly better memory for OLM than mice given pLVX-EV control virus (Two-way ANOVA: virus x session interaction, (F(1,29) = 7.15, p < 0.05), Sidak’s post hoc tests, **p < 0.01, ***p < 0.001, n = 16, 15, all males). d Total exploration was similar for both groups at test (t(29) = 0.57, p = 0.57). e Schematic of CRISPR/dCas9 Synergistic Activation Mediator (SAM) system used to drive Per1 transcription. Top: Individual components of SAM. Bottom: Components assembled at the Per1 promoter, driving Per1 transcription. f Per1 mRNA was significantly increased 48 h after transfection of CRISPR-SAM components in HT22 cells compared to cells transfected with the control sgRNA (Two-way ANOVA: Group x Timepoint interaction (F(1,8) = 14.77, p < 0.01), Sidak’s post hoc tests, **p < 0.001, n = 3,3,3,3). g 18-m.o. mice given hippocampal infusions of the CRISPR-SAM system with sgRNA targeting Per1 showed significantly better memory for OLM compared to EV control mice with control sgRNA (Two-way ANOVA: Virus x Session interaction (F(1,30) = 5.83, p < 0.05), Sidak’s post hoc tests, ***p < 0.001, n = 17, 15, all males). h Total exploration was similar for both groups at test (t(30) = 0.41, p = 0.68). Data are presented as mean ± SEM
