Fig. 5: ΔFosB orchestrates gene expression in NAc-projecting vHPC neurons.
From: Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance
a Experimental design for circuit-specific TRAP. Retrograde Cre vector is injected into NAc and vHPC is harvested for immunoprecipitation of ribosomes from L10-GFP-expressing NAc-projecting cells and sequencing of actively translating mRNA. b Sequencing reads (red or green peaks) for FosB gene (exons indicated by thick blue bars beneath graph) from WT (FosB+/+) and FosB KO (FosBfl/fl) vHPC-NAc neuron mRNA. c ΔFosB overexpression in Neuro2A cells regulates mRNA expression of some TRAP-identified target genes. *P = 0.0240 for Adra2a, #P = 0.0914 for Nefm, #P = 0.0815 for Prkcb (independent samples t-test compared to Control Transfection; Adra2a n = 12 plates/group; Arhgap36 n = 6; Elavl2 n = 6; Kctd9 n = 5–6; Nefm n = 12; Gaa n = 6; Igfbp6 n = 6; Peg10a n = 6; Peg10b n = 6; Prkcb n = 6; Scg5 n = 6). d Adra2a mRNA expression is increased in Neuro2A cells transfected with ΔJunD or FosB-specific gRNA and Cas9 (Cas9). *P = 0.0133, #P = 0.0822 (n = 12 wells/group; one-way ANOVA with Holm–Sidak post-tests versus control). e Representative coronal vHPC images (20X) showing NAc-projecting neurons expressing GFP (green) and α2AAR (red) in floxed FosB KO (FosBfl/fl; bottom panels) and WT (FosB+/+; top panels) mice. f Intensity of α2AAR expression in NAc-projecting GFP-labeled is decreased by FosB KO (FosBfl/fl). *P < 0.0001 (n = 100 FosB+/+ cells, n = 83 FosBfl/fl cells; independent samples t-test compared to FosB+/+). e Proposed model: in resilient mice, stress strongly induces ΔFosB in vHPC-NAc neurons initiating gene expression that underlies a protective decrease in excitability of the projection; in susceptible mice, a lack of FosB expression allows stress-associated differential gene expression to keep vHPC-NAc excitability high, driving social avoidance. All graphs are represented as mean ± SEM.
