Autism-like atypical face processing in Shank3 mutant dogs

Atypical face processing is a neurocognitive basis of social deficits in
autism spectrum disorder (ASD) and a candidate cognitive marker for the
disease. Although hundreds of risk genes have been identified in ASD, it
remains unclear whether mutations in a specific gene may cause ASD-like
atypical face processing. Dogs have acquired exquisite face
processing abilities during domestication and may serve as an effective
animal model for studying genetic associations of ASD-like atypical face
processing. Here, we showed that dogs with Shank3 mutations
exhibited behavioral and attentional avoidance of faces, contrasting with
wild-type controls. Moreover, neural responses specific to faces (versus
objects) recorded from the electrodes over the temporal
cortex were significantly decreased and delayed in
Shank3 mutants compared to wild-type controls. Cortical responses
in the frontal/parietal region underlying categorization of faces by
species/breeds were reduced in Shank3 mutants. Our
findings of atypical face processing in dogs with Shank3 mutations provide
a useful animal model for studying ASD mechanisms and treatments.

非典型面孔加工是孤独症谱系障碍（ASD）患者社交缺陷的神经认知基础，同时也是该疾病的潜在认知标志物。尽管目前已在ASD中鉴定出数百个风险基因，但仍不清楚特定基因的突变是否会引发类ASD的非典型面孔加工。犬类在驯化过程中演化出了精湛的面孔加工能力，可作为研究类ASD非典型面孔加工遗传关联的有效动物模型。本研究发现，携带Shank3突变的犬类表现出对面孔的行为与注意回避，与野生型对照组形成鲜明对比。此外，与野生型对照组相比，Shank3突变体颞叶皮层（temporal cortex）电极记录到的面孔特异性神经反应（相较于物体）显著减弱且延迟。负责按物种/品种对面孔进行分类的额顶叶区域（frontal/parietal region）皮层反应在Shank3突变体中有所减弱。本研究中，携带Shank3突变的犬类表现出非典型面孔加工的实验结果，为研究ASD的发病机制与治疗手段提供了极具价值的动物模型。