Autism sensory dysfunction in an evolutionarily conserved system

TY - JOUR

T1 - Autism sensory dysfunction in an evolutionarily conserved system

AU - Vilidaite, Greta

AU - Norcia, Anthony M

AU - West, Ryan John Hatcher

AU - Elliott, Christopher John Hazell

AU - Pei, Francesca

AU - Wade, Alexander Robert Patrick

AU - Baker, Daniel Hart

N1 - This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2018/12/12

Y1 - 2018/12/12

N2 - 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.

AB - 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.

KW - autism

KW - animal model

KW - Drosophila

KW - sensory processing

KW - visual system

UR - http://www.scopus.com/inward/record.url?scp=85059799950&partnerID=8YFLogxK

U2 - 10.1098/rspb.2018.2255

DO - 10.1098/rspb.2018.2255

M3 - Article

C2 - 30963913

SN - 0962-8452

VL - 285

SP - 20182255

JO - Proceedings of the Royal Society B: Biological Sciences

JF - Proceedings of the Royal Society B: Biological Sciences

IS - 1893

M1 - 20182255

ER -