ESM from Autism sensory dysfunction in an evolutionarily conserved system

There is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here, we instead assay another functional domain—sensory processing—known to be affected in autism to test a novel genetic autism model in Drosophila melanogaster. We show similar visual response alterations and a similar development trajectory in Nhe3 mutant flies (total N  =  72) and in autistic human participants (total N = 154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.

越来越多的证据表明自闭症具有明确的遗传基础，学界已开发出多种遗传模型，试图在动物体内复刻自闭症相关症状。然而，当前主流的动物行为范式极少能匹配自闭症患者所表现出的社交与认知行为特征。为此，我们转而检测自闭症患者中已知受影响的另一功能域——感觉加工——以检验一种新型黑腹果蝇（Drosophila melanogaster）自闭症遗传模型。我们在Nhe3突变果蝇（总样本量N=72）与自闭症人类受试者（总样本量N=154）中，观察到相似的视觉反应改变与发育轨迹。我们发现，成年突变果蝇在接受稳态刺激时，其一阶与二阶电生理视觉反应出现分离，这一模式与自闭症谱系障碍（Autism Spectrum Disorder，ASD）成年人类群体，以及大样本量携带高自闭症特质的典型发育人群的反应模式极为相似。我们将该现象归因于瞬时视觉动态中由遗传驱动的选择性信号改变。与成年群体不同，自闭症儿童的一阶视觉反应出现减弱，这与果蝇模型的表现一致，提示视觉加工过程在发育阶段存在代偿性变化。本研究结果首次提供了一种在视觉加工中存在差异性发育表型的自闭症动物模型。