Figure 2.
CaMKIIβ activation in the vCA1 drives stress resilience and has antidepressant-like effect
(A) AAV vectors engineered to overexpress a control construct (AAV-GFP), CaMKIIβ (AAV-CaMKIIβ), or a constitutively active form of CaMKIIβ (AAV-CaMKIIβ-CA). ITR, inverted terminal repeats; PCamk2a, Camk2a promoter; WPRE, woodchuck hepatitis virus posttranscriptional regulatory element.
(B) Experimental timeline for chronic stress and behavioral testing. CUMS, chronic ultra-mild stress; SIT, social interaction test; SPT, sucrose preference test; FST, forced swim test.
(C) Schematic representation showing the microinjection of AAV into the vCA1 region of mice. Region-specific expression of GFP in vCA1 but not dCA1 is shown. Scale bar, 500 μm.
(D–F) BALB mice overexpressing CaMKIIβ or CaMKIIβ-CA show significantly increased social interaction time in the SIT (D), increased sucrose preference in the SPT (E), and decreased immobility time in the FST (F) under stress. n = 12–13 mice per group.
(G) CaMKIIβ-CA overexpression prevents CUMS-induced reduction of Fos expression in the vCA1 of BALB mice. n = 6 mice per group.
(H) AAV-mediated spatiotemporal gene expression strategy using a cocktail of AAV-Camk2a-tTA and AAV-TRE-CaMKIIβ-CA or AAV-TRE-GFP.
(I) Experimental timeline for CaMKIIβ-CA overexpression after the termination of CUMS episodes. BALB mice were treated with doxycycline (dox) after AAV injection and exposed 21 days later to CUMS for 6 weeks; they were then taken off dox, and 4 days later behavioral tests were performed.
(J) AAV microinjection into the vCA1 region. Region-specific and dox-regulated expression of GFP in the vCA1 is shown. Scale bar, 200 μm.
(K–M) CaMKIIβ activation after CUMS leads to a significant increase in social interaction time in the SIT (K), a tendency for increased sucrose preference in the SPT (L), and reduced immobility time in the FST (M). n = 15–16 mice per group.
One-way ANOVA followed by a Tukey's post hoc test (in D-G) and two-tailed Student's t-test (in K-M) were used for statistical analyses. ∗p < 0.05. Bar graphs show mean ± SEM.
See also Figure S2. Complete statistical summaries are provided in Table S2.