Fig. 7: Sleep-specific inhibition of a V1 engram disrupts visually cued fear memory consolidation.

a cfos::ArchT mice implanted with bilateral V1 optical fibers and EEG/EMG electrodes were presented with X° for TRAP. Eleven days later, mice were conditioned using either the same orientation (X°) or an alternate orientation (Y°) as the shock cue. Post-conditioning, the mice slept with sleep-specific inhibition during the first 6 h. b No-inhibition (non-opsin-expressing) controls (n = 8) and mice cued to Y° with subsequent optogenetic inhibition (n = 8) showed higher freezing responses to the shock cue vs. the neutral cue (two-way RM ANOVA: main effect of optogenetic manipulation condition, F = 10.247, p < 0.001, main effect of orientation, F = 10.679, p = 0.004, optogenetic condition × orientation interaction, F = 7.359, p = 0.004, no-inhibition control—p = 0.002, Y°-cued inhibition—p = 0.003, Holm–Sidak post hoc test). In contrast, mice cued to X° with subsequent optogenetic inhibition (n = 8) did not differ in freezing responses to the shock cue vs. the neutral cue (N.S., Holm–Sidak post hoc test). Mice cued to either X° or Y° with subsequent inhibition showed higher freezing responses to both cues relative to no-inhibition controls, indicative of generalization. c Controls and mice cued to Y° show significant discrimination, while mice cued to X° did not (*p = 0.016 for both no-inhibition control and Y° cued with inhibition; Wilcoxon signed-rank test). Values in b, c indicate mean ± SEM.