1 Department of Psychology, Stanford University , Stanford, CA 94305 , USA.
3 Department of Biology, University of York , York YO10 5DD , UK.
Proc Biol Sci. 2018 Dec 19;285(1893):20182255. doi: 10.1098/rspb.2018.2255.
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很强的遗传基础,许多遗传模型正在被开发,试图在动物身上复制自闭症症状。然而,目前的动物行为范式很少能与自闭症个体表现出的社会和认知行为相匹配。在这里,我们转而检测另一个功能领域——感觉处理,已知该领域在自闭症中受到影响,以测试果蝇中的一种新的遗传自闭症模型。我们发现 Nhe3 突变果蝇(总数为 72 只)和自闭症人类参与者(总数为 154 名)表现出相似的视觉反应改变和相似的发展轨迹。我们报告说,成年突变果蝇对稳态刺激的第一级和第二级电生理视觉反应之间存在分离,这与 ASD 成年人类以及具有大量自闭症特征的大量神经典型个体的反应模式非常相似。我们将其解释为瞬时视觉动态中遗传驱动的选择性信号改变。与成年人不同,自闭症儿童的第一级反应下降,与果蝇模型相匹配,这表明在发育过程中发生了处理的补偿性变化。我们的研究结果提供了第一个包含视觉处理中差异发育表型的自闭症动物模型。