HPC input to the mPFC is required for theta coupling and recognition memory. A, Experimental paradigm. AAV expressing ArchT-GFP was delivered to the CA1 HPC with tdTomato as the marker. Picture on the right show transduced pyramidal neurons in area CA1 of the indicated region (red square). B, Images show terminal GFP labeling in the mPFC at the indicated bregma. C, Schematic shows the behavioral task during training and test. The HPC-to-mPFC input was inhibited during the two NOR tests with 1 min bins (light-on/light-off cycle). D, Heat maps of the exploratory behavior of a representative rat (with ArchT expression) during the light-off (left) and light-on (right) phases in the NOR test session. E, The discrimination index was significantly reduced by light stimulation in the ArchT group (two-way ANOVA with Bonferroni's multiple-comparison test: ArchT group: *p < 0.05, N = 13; control group: p > 0.05, N = 11) during the light-on phases. F, The total object exploration time in the Arch group and control group (two-way ANOVA with Bonferroni's multiple-comparison test: ArchT group: p > 0.05, N = 13; control group: p > 0.05, N = 11). G, The familiar exploration time (left) did not change between the light-off and light-on phases (two-way ANOVA with Bonferroni's multiple-comparison test: ArchT group: p > 0.05, N = 13; control group: p > 0.05, N = 11), but the novel object exploration time (right) was significantly reduced during the light-on phases (two-way ANOVA with Bonferroni's multiple-comparison test: ArchT group: *p < 0.05, N = 13; control group: p > 0.05, N = 11). H, The distance traveled (left) and velocity (right) during the light-off and light-on phases (two-way ANOVA with Bonferroni's multiple-comparison test: ArchT group: distance traveled, p > 0.05, N = 13; control group: distance traveled, p > 0,05, N = 11; velocity, p > 0.05, N = 11). I, Left, Inhibiting the HPC → mPFC projection did not change HPC–mPFC theta coupling during familiar object exploration but significantly reduced HPC–mPFC theta coupling during NOR in the ArchT group (three-way ANOVA with Bonferroni's multiple-comparison test; ArchT group: familiar object, p > 0.05, n = 10 test sessions; novel object, *p < 0.05, n = 10 test sessions; control group: familiar object, p > 0.05, n = 10 test sessions; novel object, p > 0.05, n = 10 test sessions). Values are the mean ± SEM. N represents the number of rats.