Hirofumi Asano ¹ Masaya Arai ¹ Aito Narita ¹ Mamoru Fukuchi ² Soichi Oya ¹ Yuhei Yoshimoto ¹ Goichi Miyoshi ^1*

• ¹ Graduate School of Medicine, Gunma University, Maebashi, Japan
• ² Takasaki University of Health and Welfare, Takasaki, Gunma, Japan

Autism spectrum disorder (ASD) is characterized by social deficits and restricted behaviors, with developmental defects in GABAergic circuits proposed as a key underlying etiology. Here, we introduce the V-Y assay, a novel space preference test in which one arm of the Y-maze is initially hidden and later revealed as a novel space. Using an ASD mouse model with FOXG1 haploinsufficiency, which exhibits ASD-like social impairments that can be either exacerbated or ameliorated by GABAergic circuit manipulations, we observed impaired novel space preference and exploratory behavior in the V-Y assay. Interestingly, unlike social phenotypes, novel space preference was initially established by three weeks of age but regressed by six weeks. Furthermore, alterations in GABAergic signaling via Gad2 mutation did not affect novel space preference, in contrast to their impact on social behaviors. These findings reveal that the regression of novel space preference in ASD follows a distinct developmental trajectory from GABA-driven social impairments, providing new insights into the mechanisms underlying ASD.