Asano Hirofumi, Arai Masaya, Narita Aito, Kuroiwa Takayuki, Fukuchi Mamoru, Yoshimoto Yuhei, Oya Soichi, Miyoshi Goichi
Department of Developmental Genetics and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Front Cell Neurosci. 2025 Jan 15;18:1513347. doi: 10.3389/fncel.2024.1513347. eCollection 2024.
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 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 3 weeks of age but regressed by 6 weeks. Furthermore, alterations in GABAergic signaling via 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.
自闭症谱系障碍（ASD）的特征是社交缺陷和行为受限，γ-氨基丁酸能（GABAergic）神经回路的发育缺陷被认为是关键的潜在病因。在此，我们介绍V-Y试验，这是一种新型的空间偏好测试，其中Y迷宫的一个臂最初是隐藏的，后来作为一个新空间被揭示。使用一种具有单倍体不足的ASD小鼠模型，该模型表现出类似ASD的社交障碍，可通过GABAergic神经回路操作使其加重或改善，我们在V-Y试验中观察到新空间偏好和探索行为受损。有趣的是，与社交表型不同，新空间偏好最初在3周龄时建立，但在6周龄时消退。此外，与对社交行为的影响相反，通过突变改变GABAergic信号传导并不影响新空间偏好。这些发现表明，ASD中新空间偏好的消退遵循与GABA驱动的社交障碍不同的发育轨迹，为ASD的潜在机制提供了新的见解。
