Figure 2. Phase 1 cued fear conditioning in female and male mice, collapsed across swim condition.

Female (A-E) wildtypes are represented by teal solid lines, and female heterozygotes are represented by blue dashed lines. Male (F-J) wildtypes are represented by orange solid lines, and male heterozygotes are represented by yellow dashed lines. Fear conditioning commenced 4 weeks prior to swim stress exposure for Phase 1. Mice were trained on Day 0 in Context A by pairing five 4 kHz, 30 s tones with a 1 s, 0.8 mA foot shock that co-terminated with the tone (A,F), each pairing separated by a 90 s inter-tone interval (ITIs). Two days later (Day 2), mice were placed in Context B, where they were presented with fifteen 30 s tones with 30 s ITIs, starting after a 2 min baseline (B,G). This served as cued fear expression testing as well as cued fear extinction training; two days thereafter, mice underwent the identical procedure for the purposes of testing extinction retention (Day 4; C,H) One day later, mice were placed in Context A, and in the absence of any tones for 10 min, were tested for context fear expression (D,I). Immediately after these 10 min, five 4 kHz tones were played with 30 s ITIs in the absence of any foot shock to evaluate cued fear renewal (E,J). Data are percent time spent freezing for each 30 s period indicated. Female wildtypes, n=20; female heterozygotes, n=19; male wildtype training, n=25; male heterozygous training, n=33; male wildtype cued expression testing and extinction training, n=25; male heterozygous cued expression testing and extinction training, n=33; male wildtype extinction retention testing, n=25; male heterozygous extinction retention testing, n=32; male wildtype context fear expression, n=23; male heterozygous context fear expression, n=30; male wildtype cued fear renewal, n=22; male heterozygous cued fear renewal, n=31. Data are graphed as mean ± 95% confidence interval. *p=0.027, *p=0.042, *p=0.016 (left to right, panel B); *p=0.021 (panel F); **p=0.002 (panel B); indicate difference between heterozygous and wildtype within same sex at the indicated timepoint.