Figure 5.

Selective ablation of cortical SST neurons reduces anxiety-like behavior and overall emotionality under baseline and chronic stress conditions. (a) Design of DTA-mCherry AAV employing the DIO strategy, which uses two pairs of heterotypic, antiparallel loxP recombination sites to achieve cre-mediated transgenes inversion and expression under the control of CAG promoter. L-ITR: left-inverted terminal repeat, CAG: CMV early enhancer/chicken beta actin, WPRE: woodchuck hepatitis virus posttranscriptional regulatory element, R-ITR: right-inverted terminal repeat. (b) Schematic of the experimental design used to study the effect of SST cells suppression on behavior. Mice were tested twice: before (baseline) and after unpredictable chronic stress paradigm (UCMS). (c) Illustration of GFP (green) and DAPI (blue) immunostaining in the vehicle-control side and following 1, 2, and 3 weeks of DTA injection. The quantification of GFP cells 1, 2, and 3 weeks after DTA injection expressed as the percent of control (n=3 per condition) is shown to the right. Scale bar: 100 μm. Behavioral results associated with genetic ablation of SST cells under baseline condition (d) and after UCMS (e). Note that the longitudinal aspects of the study (pre- and post-stress in same cohorts), rather than cross-sectional, preclude direct comparison of pre- vs post-stress effects, as variations in baseline behavior 6–7 weeks apart frequently occur and could be misconstrued here as ‘stress effect' if presented together. Instead the contrasts of interest ‘DTA vs control treatments' are presented under baseline and stress conditions. (*p<0.05, **p<0.01, ***p<0.001 n=13/14 mice per group; data are mean±SEM). A full color version of this figure is available at the Neuropsychopharmacology journal online.