Environmental context modulates sociability in ube3a zebrafish mutants via alterations in sensory pathways.

Scientists studied zebrafish with a genetic change linked to autism and Angelman syndrome. They found that the fish's social behaviour changed depending on their environment - they showed more autism-like behaviours in a stressful setting but improved in a calmer environment. The research suggests that changing the environment, particularly visual aspects, might help reduce anxiety and improve social interaction in individuals with autism.

This zebrafish study investigated how environmental factors influence social behaviour in ube3a mutants, a genetic model linked to Angelman syndrome and ASD. Researchers tested mutant fish in two environments: an aversive Styrofoam container and a preferred Plexiglass setting. Mutant fish showed abnormal social behaviour in the Styrofoam environment but improved behaviour in the Plexiglass setting. The study found elevated anxiety levels in mutants and identified altered brain activation patterns.

RNA sequencing revealed upregulation of vision-related genes and altered sensory pathways, suggesting abnormal visual processing increases anxiety and reduces social interaction in stressful environments. The findings highlight how environmental context can modulate genetically predisposed ASD-like behaviours.

Findings suggest that environmental modifications, particularly those addressing sensory processing and visual stimuli, may be valuable therapeutic approaches for individuals with ASD. This supports the development of sensory-aware environments and interventions targeting environmental factors to improve social behaviour.

Study conducted in zebrafish model which may not fully translate to human ASD. Sample size not reported. Environmental manipulations were limited to container materials. Long-term effects of environmental changes not assessed.

Individuals with autism spectrum disorder (ASD) have a greater prevalence of deficits in social interactions and repetitive behaviours, which are influenced by hereditary and environmental factors. How environmental factors influence genetically predisposed individuals remains unknown. Here, we provide new evidence of the interplay between social behaviour and environmental influences, by manipulating perceived safety and threat levels in ube3a mutant zebrafish, a mutation that is linked to Angelman syndrome and ASD. Mutant fish demonstrated abnormal social behaviour in an aversive custom-made Styrofoam container, whereas these abnormalities ameliorated in a preferred Plexiglass setting.

Our findings were further supported by elevated anxiety levels in the mutants when they performed conventional anxiety-related tests, such as the light‒dark test (LDT) and the novel tank diving test (NTT). Additionally, neural activity mapping using c-Fos in situ hybridization revealed differences in activation patterns in the brains of the mutants. Importantly, we performed an overrepresentation analysis (ORA) using RNA sequencing data from ube3a mutants and integrating datasets from human diseases. We identified the upregulation of vision- and comorbidity-related genes in ube3a mutants and alterations in sensory pathways, highlighting that abnormal processing of visual information is the cause of increased anxiety levels, resulting in decreased social interaction in a stressful Styrofoam environment.

Our findings underscore the crucial impact of environmental factors on social behaviour and indicate that therapeutic options for ASD that focus on adjusting environmental contexts to modify perceived stimuli may ameliorate ASD-like behaviours.