Abstract
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.
Highlights
Autism spectrum disorder (ASD) has a strong genetic basis with a large number of genes implicated [1,2,3,4,5]
This result shows a relationship between the amplitude of the second harmonic response and the severity of the subclinical ASD phenotype; this effect cannot be directly generalized to clinical autism as the Autism Spectrum Quotient (AQ) is not diagnostic of full-blown ASD
We found sensory-processing alterations in our Drosophila model of ASD that were consistent with similar response alterations in human data at two stages of development
Summary
Autism spectrum disorder (ASD) has a strong (albeit complex) genetic basis with a large number of genes implicated [1,2,3,4,5]. In addition to the defining social and behavioural features of ASD, autistic individuals report a host of sensory symptoms including unusual sensory interests as well as hyper- and hyposensitivity to intense stimuli such as bright lights or loud noises [14,15] These human ASD sensory-processing symptoms have been well-documented behaviourally [16 –18], with electroencephalography (EEG) [16,17] and neuroimaging [19], and can be measured in animals using equivalent methods [20]. To assess the functionality of the visual system in these species, we measured steady-state visually evoked potentials (ssVEPs) to temporally modulated contrast stimuli During this paradigm, a stimulus flickered on/off at a particular frequency (for example, 12 Hz) while neural responses were recorded from the organism. To investigate the progression of ASD sensory atypicalities over the course of development, we measured visual responses at two stages of fruit fly maturation and acquired similar responses from autistic children and adults. As the ASD phenotype is complex and non-binary, we validated our sensory model with a large sample of neurotypical participants with high and low numbers of autistic traits
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