Figure 1.

Differential regulation of CaMKIIβ activity in the vCA1 of stress-susceptible and stress-resilient mouse strains

(A) Experimental timeline for chronic ultra-mild stress (CUMS) and behavioral testing. SIT, social interaction test; SPT, sucrose preference test; FST, forced swim test; NS, non-stress control.

(B–D) BALB mice show significantly reduced social interaction time in the SIT (B), reduced sucrose preference in the SPT (C), and increased immobility time in the FST (D) following CUMS. n = 24 mice per group.

(E) Experimental timeline for CUMS, imipramine (IMI) treatment, and behavioral testing. IMI was dissolved in the drinking water and administered during the last 3 weeks (IMI-21d) or 5 days (IMI-5d) of the CUMS session and during behavioral assays.

(F–H) Chronic treatment with IMI prevents CUMS-elicited behavioral abnormalities in the SIT (F), SPT (G), and FST (H). n = 16 mice per group.

(I) Experimental timeline for subchronic and mild social defeat stress (smSDS) and behavioral testing.

(J–L) BALB mice show significantly reduced time spent in the target zone (J) and increased time spent in the corner zone (K) in the SIT, and decreased sucrose preference in the SPT (L), following smSDS. n = 39–48 mice per group.

(M and N) Representative coronal slices showing Fos-positive cells in the ventral CA1 (vCA1) region (M). CUMS reduces Fos expression in the vCA1 region of BALB, but not B6 mice (N). n = 8 mice per group. Scale bar, 100 μm.

(O) Specific brain regions were isolated from brain tissue sections using tissue punch (dCA1 and vCA1). Scale bar, 1 mm.

(P) Gene expression profiling for CaMK family members within the vCA1 showing reduced Camk2b expression in BALB mice following CUMS (n = 6 mice per group).

(Q) Increased Camk2b expression following chronic treatment with IMI (n = 8 mice per group).

(R and S) Downregulation of CaMKIIβ expression in BALB mice and increased phosphorylation of CaMKIIβ (T287) in B6 mice following CUMS (n = 8 mice per group).

(T) Q-PCR data showing reduced Camk2b expression in BALB mice following smSDS. n = 8 mice per group.

(U and V) Downregulation of CaMKIIβ expression in BALB mice and increased phosphorylation of CaMKIIβ (T287) in B6 mice following smSDS (n = 6–8 mice per group).

two-way ANOVA followed by a Tukey's post hoc test (in B, D, J, K, N, S, T, P and V), Kruskal-Wallis test followed by a Dunn's multiple comparison (in C and L), one-way ANOVA followed by a Tukey's post hoc test (in F-H, and Q), and multiple comparisons (in P) were used for statistical analyses. ∗p < 0.05. Bar graphs show mean ± SEM.

See also Figure S1. Complete statistical summaries are provided in Table S2.