Fig. 5: dDG interference is specific to the fear memory and does not affect other hippocampal-mediated memories.

a Viral strategy and experimental design. We randomly labeled a dDG ensemble and then trained water-restricted mice to obtain water from one of the arms in an 8-arm radial maze (4 trials/day). Following criterion, they were FC and 3 h later tested on spatial memory. The next day they received a recall test during which labeled cells were stimulated. Half the mice received one reminder session (trial 1, T1) 5 min prior to recall, and trials 2–4 (T2–4) 3 h after recall. The other half did not receive a reminder session, and instead all 4 regular trials 3 h after recall. Spatial performance was tested the next day, 3 h before the first EXT session. The next day mice got a second EXT session and 3 h later a curtain probe. The next day, mice underwent IS and 24 h later a RE test. Effect of dDG Stimulation on Fear Memory: b During FC, all mice froze post-shock (three-way RM ANOVA: F(1,16) = 377.1, P < 0.0001). c During recall, stimulation decreased freezing in the No Reminder-ChR2 group (P = 0.0027) compared to eYFP controls (three-way RM ANOVA: F(1,16) = 26.11, P = 0.0001, Time; F(1,16) = 24.75, P = 0.0001, Virus). d Freezing decreased across EXT days and in ChR2 groups compared to eYFP controls (three-way RM ANOVA: F(1,16) = 6.008, P = 0.0261, Time × Virus). More specifically, in No Reminder groups on day 1 (P < 0.0001) and in both Reminder (P = 0.0279) and No Reminder (P = 0.0395) groups on day 2. e No group differences seen during IS. f During RE, mice in both Reminder (P = 0.0008) and No Reminder (P = 0.0003) ChR2 groups froze less compared to eYFP controls (two-way ANOVA: F(1,16) = 53.27, P < 0.0001). g and at RE compared to IS (three-way RM ANOVA: F(1,16) = 66.81, P < 0.0001, Virus × Day). Effect of dDG Stimulation on the Spatial Memory: h Mice reached criterion in 5–14 days. Dependent measures: i, j latency to find reward, k, l arm-deviations, m, n reference errors, and o, p repeated reference errors. During acquisition (left panels, first 3 and last 3 days of training), for T1 (long-term memory) and T2–4 (short-term memory) all mice improved across training (three-way RM ANOVAs. Latency - T1: F(5,48) = 8.053, P < 0.0001, T2–4: F(5,48) = 19.66, P < 0.0001; Arm-Deviations - T1: F(5,48) = 6.817, P < 0.0001, T2–4; F(5,48) = 5.186, P = 0.0007; Reference Errors - T1: F(5,48) = 3.921, P = 0.0046, T2–4: F(5,48) = 14.94, P < 0.0001; Repeated Reference Errors - T1: F(5,48) = 6.392, P = 0.0001, T2–4: F(5,48) = 9.848, P < 0.0001). We compared spatial performance after FC (purple), before (Reminder groups only) and after recall (pink), and before EXT1 (mint) (middle panels). We only saw differences for arm-deviations. For T1, both ChR2 and eYFP-mice in the Reminder groups had higher arm-deviations during the first trial prior to EXT1 (three-way RM ANOVA: F(1,24) = 4.741, P = 0.0395). As differences were not between ChR2 and eYFP mice, this suggests the Reminder session, and not the reconsolidation-based manipulation, briefly affected this measure. Briefly since, on T2–4: mice in the ChR2 groups (Reminder and No Reminder) demonstrated better performance (fewer arm-deviations) compared to eYFP groups on EXT 1, suggesting the manipulation improved performance on the maze despite whether a reminder session was given (three-way RM ANOVA: F(1,24) = 6.819, P = 0.0153). For the curtain probe, extra-maze cues were not visible. We compared performance on this test to the first and last 3 days of acquisition (peach) (right panels). All mice performed as poorly as the start of training (three-way RM ANOVAs. Latency - T1: F(2,24) = 15.16, P < 0.0001, T2–4: F(2,24) = 43.93, P < 0.0001; Arm-Deviations - T1: F(2,24) = 5.671, P = 0.0096, T2–4; F(2,24) = 8.610, P = 0.0015; Reference Errors - T1: F(2,24) = 13.80, P = 0.0001, T2–4: F(2,24) = 6.009, P < 0.0077, Time × Reminder; Repeated Reference Errors - T1: F(2,24) = 7.927, P = 0.0023, T2–4: F(2,24) = 5.862, P = 0.0085, Time × Virus). Dotted lines: criterion required for 2 consecutive days. Data represented as means ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.00. dDG dorsal dentate gyrus, CP curtain probe, EXT extinction, F3 first 3 days, IS immediate shock, L3 last 3 days, RE reinstatement. Source data provided as a Source Data file.