Figure 4.

GABA_ARs act during development to control trait anxiety. a–c, Heightened anxiety-related behavior of Emx1Cre × fγ2/+ mice. In the free-choice exploration test (a), Emx1Cre × fγ2/+ mice made more retractions from entering a novel unit after the removal of the partition (U = 10.5; p < 0.01; n = 8–10 per genotype), and, once they entered, they spent less time in the novel compartment (U = 8; p < 0.01) than fγ2/+ littermate controls. The mean number of familiar units visited was similar in the two groups (U = 28.5; NS). In the light–dark choice test (b), the mean time spent in the lit area was significantly lower in Emx1Cre × fγ2/+ (n = 9) than in fγ2/+ littermate control mice (n = 22) (p < 0.05, least significant difference test after unweighted mean genotype × area ANOVA with area as within-subject factor, F_(1,29) = 4.0; p = 0.05). The group difference was not significant for the mean number of light–dark transitions (t_(13.17) = 1.8; p < 0.1, t test with separate variances). In the elevated plus maze (c), the mean proportion of both entries and time spent on the open arms over 5 min were decreased in Emx1Cre × fγ2/+ compared with littermate control mice (U = 19.5 and 20, respectively; p < 0.01; n = 10–14 per genotype). d–f, The anxiety-related behavior of CaMKIICre2834 × fγ2/+ mice and littermate fγ2/+ controls was tested under the same conditions. In the free-choice exploration test (d), CaMKIICre2834 × fγ2/+ mice behaved as controls with respect to mean number of retractions (t_(36.99) = 1.5; n = 22–30 per genotype) and mean time spent in the novel compartment (t_(45.58) = 0.3). In the light–dark choice test (e), CaMKIICre2834 × fγ2/+ mice were indistinguishable from controls for the mean time spent in the lit area and the mean number of light–dark transitions (U > 34; n = 10 per genotype). In the elevated plus maze (f), CaMKIICre2834 × fγ2/+ mice did not differ from controls with respect to the mean proportion of entries and time spent on the open arms and the number of closed arm entries (t₍₃₄₎ ≤ 0.7; n = 18 per genotype). All experiments were performed with females reared in group-housed cages. Data are representative of two to four experiments each. Values shown represent group means ± SEM. g–i, The anxiety-related behavior of 4- to 6-month-old CaMKIICre2834 × fγ2/+ mice was assessed as in d–f. In the free-choice exploration test (g), 6-month-old CaMKIICre2834 × fγ2/+ were indistinguishable from fγ2/+ littermate controls with respect to the number of retractions from entering a novel unit, the total time spent in the novel units, and the number of familiar units visited (for the three variables, U > 60; n = 9–16 per genotype). Behavior in the light–dark choice test (h) of CaMKIICre2834 × fγ2/+ mice (n = 7) assessed at 4 months of age, mice did not differ from fγ2/+ (n = 21) with respect to both the total time spent in the lit area and the number of light–dark transitions (U > 45). Similarly, behavior in the elevated plus maze (i) of 4-month-old CaMKIICre2834 × fγ2/+ mice (n = 7) was indistinguishable from fγ2/+ littermates (n = 21) with respect to the number of open and closed arm entries and time spent on the open arms (U > 38). Data represent means ± SEM.