Figure 5. The AV→RSC Circuit Regulates Memory Specificity.

(A) Halorhodopsin (NpHR) expression in AV, C1QL2 staining (red).

(B) AV cell bodies or AV→RSC terminal inhibition during CFC training (day 1) followed by LTM recall and neutral context tests (control eGFP n = 8 mice, AV NpHR n =10 mice, AV→RSC NpHR n = 8 mice).

(C) cFos staining in RSC using home cage (n = 4 mice), training control (eGFP, n = 5 mice), training AV→RSC NpHR-eYFP (n = 5 mice) groups.

(D) Retrograde RV tracing in PV-Cre, somatostatin (SST)-Cre, or VIP-Cre mice. Images show RV labeling in AV thalamus (left), quantification of RV⁺ cells in AV (n = 4 mice per group) (right). Normalized starters across groups.

(E-G) cFos activation of PV, VIP cell types in RSC during CFC training, representative images (E-F), overlap quantification (G) (PV-Cre: home cage n = 7 and training n = 8 mice, VIP-Cre: home cage n = 5 and training n = 7 mice). Cre mice were prepared by injecting a Cre-dependent eYFP virus in RSC.

(H) Fold change plotted relative to average home cage counts (n = 8 PV-Cre training mice, n = 7 VIP-Cre training mice).

(I-J) AV→RSC inhibition with PV or VIP activation in RSC during training, viral injection schematic (I), neutral context test (J) (PV-Cre: C21 n = 8 and C21+light n = 6 mice, VIP-Cre: C21 n = 7 and C21+light n = 6 mice).

(K-L) AD→RSC or AV→RSC terminal inhibition during training in the cocaine-induced conditioned place preference behavior. Preference for the cocaine (Coc) vs. the saline (Sal) side is plotted within animal for the recall test (K), and the modified chamber test (L) (n = 12 mice per group).

One-way ANOVA followed by Bonferroni post-hoc test (B-D), two-tailed unpaired t test (G-H, J), and paired t test (K-L). For statistical comparisons, *p < 0.05, **p < 0.01, ***p < 0.001; NS, not significant.

Data are presented as mean ± SEM.