Fig. 3: Chronic chemogenetic inhibition of PV neurons in the PL cortex led to a sustained reduction in fear memory and a persistent suppressed fear-induced high-PV shifts.

A Experimental paradigm. Mice were administered CNO daily for one week after fear conditioning, fear retrieval was tested 24 h or three weeks after the last injection. B–E Inhibition of PV neurons one week decreased the contextual (B, t (14) = 10.64, p < 0.0001) and tone-cued (C, t (14) = 10.91, p < 0.0001) fear expression, and the reduction in fear expression was still observed three weeks later (D, t (14) = 19.85, p < 0.0001; E, t (14) = 15.18, p < 0.0001). F Experimental paradigm. CNO was injected daily for one week before open field test. G Chronic inhibition of PV neurons had no effect on locomotion (t (14) = 0.9245, p = 0.3709). H, I Experimental paradigm. Following training, the animals received daily CNO administration for one week. Fear memory retrieval was tested one day or three weeks after the final CNO injection. The animals were scarified six hours following their fear retrieval test for PV staining. J–M Chronic inhibition of PV neurons before fear retrieval suppressed the high-PV shift, and the suppression was still observed three weeks later (Low-PV: K F (3,18) = 34.51, p < 0.0001; High-PV: L F (3,18) = 28.80, p < 0.0001). M The manipulation had no effect on the number of PV neurons (F (3,18) = 0.2013, p = 0.8941). B–G, unpaired two-tailed Student’s t-test, n = 8 mice for each group. K–M One-way ANOVA with Tukey multiple comparisons, n = 5-6 mice for each group. The data are presented as the mean ± SEM, **p < 0.01, ***p < 0.001.