Fig. 5: Decrease in GABAergic tone exacerbates the ASD social phenotypes of the FoxG1 Heterozygous model.

Gad2 heterozygous and null littermate animals in the background of wild type and FoxG1 Heterozygous model were analyzed by three-chamber assay. a Example traces of the animals are shown for the four genotypes. b In contrast to the Gad2 Het animals, Null animals showed ASD-like social behavioral alterations by not preferring the social side of the chamber (NS, purple) and staying in the center during the social novelty session (asterisks, purple). c Gad2 Het and Null animals in the FoxG1 Heterozygous background showed ASD like social behavioral impairments, and during social novelty session, strongly preferred to stay in the center chamber compared to the control animals. n = 22, 28, 21, 25, 29, 20 (b, c, from left to right), p = 3.56 × 10⁻⁷****, 0.000234***, 1.62 × 10⁻⁵****, 0.0452*, 0.101, 0.00577**, = 0.380, 0.676, 0.000264***, 0.156, 0.562, 0.838 (b, c, left vs right), = 0.825, 0.00781**, 0.0396*, 0.000326***, 0.000521*** (b, c, vs WT, center). d Social behavior scores of the Gad2 and FoxG1 mutant models. While the score of Gad2 nulls is comparable to the FoxG1 Heterozygous model (purple bars), Gad2 Het or Null mutations exacerbates the impaired sociability score of FoxG1 Heterozygotes (dark bars). p = 0.283, 0.00294**, 0.00738**, 1.25 × 10⁻⁷****, 6.49 × 10⁻⁶****(vs WT, from top to bottom), = 0.0188*(Gad2 WT vs Het in FoxG1 Het background). e Working memory is not affected by Gad2 mutation(s) in both wild type and FoxG1 Heterozygotes. n = 44, 56, 40, 48, 58, 40 (from left to right), p = 0.0121*(WT vs FoxG1 Het), = 0.352, 0.320, 0.339, 0.460(NS, from left to right). Data are mean ± SEM, p values are from two-tailed t-test.