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Fig. 2 | Molecular Autism

Fig. 2

From: Scn2a haploinsufficient mice display a spectrum of phenotypes affecting anxiety, sociability, memory flexibility and ampakine CX516 rescues their hyperactivity

Fig. 2

Emx1-Cre, but not Vgat-Cre-mediated conditional Scn2a KO replicates the increased vertical activity in the open field, whereas both affect anxiety-like behavior in the elevated-plus maze. Heterozygous deletion of Scn2a in dorsal-telencephalic excitatory neurons led to a mildly, yet not significantly, longer distance traveled (a) in the open field in Scn2afl/+ (fl/+); Emx1-Cre, whereas +/+; Emx1-Cre mice traveled significantly longer distances than their +/+ and fl/+ littermates (genotype-time interaction: F3,58 = 0.372, NS; time effect: F2,62 = 11.034, p < 0.001; genotype effect: F3,13 = 3.135, p < 0.05; post-hoc p+/+;Emx1_vs_+/+ < 0.01 and p+/+;Emx1_vs_fl/+ < 0.05). Fl/+; Emx1-Cre and +/+; Emx1-Cre mice spend significantly more time in the center of the open field than their +/+ littermates (b, genotype-time interaction: F6,58 = 0.784, NS; time effect: F2,62 = 7.046, p < 0.01; genotype effect: F3,13 = 2.797, p < 0.05; post-hoc pfl/+;Emx1_vs_+/+ < 0.05 and p+/+;Emx1_vs_+/+ < 0.05). The number of rearing (c) was also significantly increased in fl/+; Emx1-Cre mice compared to their +/+, fl/+ and fl/+; Emx1-Cre littermates (genotype-time interaction: F6,58 = 0.784, NS; time effect: F2,62 = 7.046, p < 0.01; genotype effect: F3,13 = 2.797, p < 0.05; post-hoc pfl/+;Emx1_vs_+/+ < 0.001, pfl/+;Emx1_vs_fl/+ < 0.05, pfl/+;Emx1_vs_+/+;Emx1 < 0.001 and p+/+;Emx1_vs_fl/+ < 0.01). In contrast, no significant differences were seen in distance traveled (d, genotype-time interaction: F6,33 = 0.394, NS; time effect: F2,37 = 22.403, p < 0.001; genotype effect: F3,10 = 1.226, NS), time spent in the center area (e, genotype-time interaction: F6,33 = 2.017, NS; time effect: F2,37 = 5.019, p < 0.01; genotype effect: F3,10 = 2.055, NS), and rearing count (f, genotype-time interaction: F6,33 = 0.247, NS; time effect: F2,37 = 1.005, NS; genotype effect: F3,10 = 1.078, NS) in fl/+; Vgat-Cre mice, harboring an inhibitory neuron specific deletion of Scn2a, compared to their control +/+, +/+; Vgat-Cre and fl/+ mice. In the elevated–plus maze task, fl/+;Emx1-Cre mice displayed a tendency and fl/+;Vgat-Cre mice a significant increase in number of entries in the open arms (g) and time spent in these open arms (h) than their respective controls (Emx1-Cre: F3,53 = 2.409, p = 0.077 in g and F3,53 = 2.348, p = 0.083 in h; Vgat-Cre: F3,46 = 5.634, p < 0.01 in g and F3,46 = 3.671, p < 0.05 in h). The significant preference for the closed arms over the open one was however conserved in fl/+;Emx1-Cre (i) as well as in fl/+;Vgat-Cre mice (j). OA open arm, C center, CA closed arm. Emx1-Cre conditional KO experiment: +/+: N = 15, +/+; Emx1-Cre: N = 15, fl/+: N = 11, fl/+; Emx1-Cre: N = 16. Vgat-Cre conditional KO experiment: +/+: N = 12, +/+; Vgat-Cre: N = 13, fl/+: N = 13, fl/+;Vgat-Cre: N = 12. Values are expressed as mean ± standard error of the mean. Statistical significance in af was assessed using two-way repeated measures ANOVA followed, when a main effect of genotype was observed, by a one-way ANOVA and a Tukey’s post-hoc test. Statistical significance in gj was assessed using one-way ANOVA across (gh) or within (i, j) groups of genotype. Significance was set at *p < 0.05, **p < 0.01, and ***p < 0.001

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