Fig. 5

CA2-specific deletion of MRs is sufficient to drive behavioral changes in both social and non-social contexts. a After a 10 min habituation period to the testing arena, mice were tested for social investigation in a three-chamber task. During a 10 min period, mice were given the opportunity to explore the arena, one chamber containing a novel, same-sex conspecific (designated with black mouse icon) and the other chamber remaining empty (designated with xxxx). b–e A main effect of chamber was found for NesCre mice (b, c) (two-way rmANOVA, F(1,29) = 33.87, p < 0.0001) and for Am2Cre mice (d, e) (two-way rmANOVA, F(1,35) = 16.7, p = 0.0002). A main effect of genotype was also found in NesCre mice (F(1,29) = 4.511, p = 0.0423). Cre⁺ and cre^– mice from both strains showed a preference for the chamber containing the mouse (open circles in c and e) compared with the empty chamber (closed circles). Post hoc analysis for empty chamber vs. mouse chamber revealed these significant differences: NesCre^–, p < 0.0001; Am2Cre^–, p = 0.0043; NesCre⁺ , p = 0.0046, Am2Cre⁺, p = 0.0096. See Supplemental Table 1 for complete statistics. f After the social investigation task, a new novel mouse was placed in the once empty chamber to test mice for their ability to discriminate between a familiar (black mouse icon) and a novel (blue mouse icon) mouse. g–j During the social discrimination task, a main effect of chamber was found for NesCre mice, primarily driven by the cre-negative mice (g, h) NesCre: two-way rmANOVA, F(1,29) = 8.03, p = 0.0083). Post hoc analysis revealed that cre-negative mice of both strains showed a preference for the unfamiliar mouse (open circles in h and j) over the familiar mouse (closed circles) (NesCre^–, p = 0.0204; Am2Cre^–, p = 0.0313); however, neither g, h NesCre⁺ (p = 0.1131) nor i, j Am2Cre⁺ (p = 0.7126) mice showed this preference. See Supplemental Table 2 for complete statistics. Panels b, d, g, and i show representative heatmaps of the duration of time spent in each chamber, and the quantification of all mice are shown in c, e, h, and j, with the representative mice designated in red. k Mice were tested for their reactivity to novel objects in a familiar testing arena. After 2 days of habituation to the testing arena (10 min each day), on Day 3 mice were given 10 min to explore 2 novel objects in the same familiar context. l, n NesCre⁺ and m, o Am2Cre⁺ mice spent more time in the investigation zones actively investigating the novel objects than did their cre-negative littermates (NesCre: two-tailed t-test, t(29) = 4.165, p = 0.0003; Am2Cre: two-tailed t-test with Welch’s correction for unequal variances, t(20.39) = 2.401, p = 0.026). Representative traces of movement around the objects are shown in l and m, with the representative animals designated in red in n and o. ^nsp > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001