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. 2020 Sep 8;11:4484. doi: 10.1038/s41467-020-17825-x

 Fig. 3. Circuit-specific vHPC ΔFosB mediates stress resilience and anxiety-like behavior.

 Fig. 3

a Schematic of ΔFosB rescue experiments in vHPC-NAc afferent neurons. Retrograde vector expressing Cre-dependent Cas9 and ΔFosB is injected into NAc while local vector expressing Cre and FosB guide gRNA is injected into vHPC. FosB silencing (KO) occurs in co-transduced vHPC-NAc neurons, and ΔFosB overexpression is also driven by Cre in the same neurons (Rescue). b ΔFosB rescue (Resc) in vHPC-NAc neurons reverses stress-induced social avoidance, indicated by enhanced social interaction ratio (left) and increased investigation of a social target (right). *P = 0.0161 for SI ratio and *P = 0.0431 for interaction time (n = 13 KO, n = 12 Resc; SI ratio: independent samples t-test compared to KO; investigation time: two-way mixed ANOVA with Holm–Sidak post-test KO No Target vs Target). c Schematic of ΔFosB rescue experiments in vHPC-BLA afferent neurons. d ΔFosB rescue in vHPC-BLA neurons reverses the anxiolytic effects of FosB silencing, decreasing open arm time in the EPM. **P = 0.0042 (n = 15 KO, n = 12 Resc; independent samples t-test compared to KO). e ΔFosB rescue also reverses avoidance learning impairment. *P = 0.0459, **P = 0.0060, ***P < 0.0001 (n = 15 KO, n = 13 Resc; two-way mixed ANOVA with Holm–Sidak post-tests compared to KO). f Schematic of ΔFosB overexpression in vHPC-NAc afferent neurons. Retrograde vector expressing Cre-dependent ΔFosB is injected into NAc while local vector expressing Cre is injected into vHPC. ΔFosB overexpression is driven by Cre only in co-transduced vHPC-NAc neurons (ΔFosB). g ΔFosB overexpression in vHPC-NAc enhances social interaction following stress, producing a resilient phenotype. *P < 0.05 (n = 18 control, n = 12 ΔFosB; SI ratio: independent samples t-test compared to control; interaction time: two-way ANOVA followed by Holm–Sidak post-test ΔFosB No Target vs Target). h Schematic of ΔFosB overexpression in vHPC-BLA afferent neurons. i, j ΔFosB overexpression in vHPC-BLA does not alter anxiety-like behavior or avoidance learning (n = 7 mice/group). All graphs are represented as mean ± SEM.