Autism spectrum disorders (ASDs), thought to arise from interactions among multiple heterogeneous genetic and environmental factors, are typically not diagnosed until early childhood, following the onset of behavioral symptoms. However, assays that tap into the pathogenic process of experience-dependent neurodevelopment may be capable of revealing synaptic plasticity deficits pre-symptomatically and could enable earlier identification and stratification of children with distinct forms of ASDs.

Teams headed by Mark Bear and Charles Nelson have observed, using highly similar protocols, that both mice and neurotypical adult humans exposed daily to phase-reversing visual images exhibit stimulus-selective behavioral habituation accompanied by long-lasting modulation of neurophysiological responses in the visual cortex. Using eye tracking and electroencephalography, Nelson’s team plans to extend this assessment to typically developing children aged 2–12 years to determine if they demonstrate similar patterns of behavioral habituation and neural modulation. Motivated by robust phenotypes in mice heterozygous for the Tsc2 gene, they will then compare measures from typically developing children to age-matched children with tuberous sclerosis complex. In tandem, Bear’s team will use this visual stimulation protocol to screen juvenile mice from four distinct genetic models of ASDs: fragile X syndrome (Fmr1^–/y), Angelman syndrome (Ube3a^m-/p+), 16p11.2 (chr7qF3) deletion and tuberous sclerosis complex (Tsc2^+/-). Identified behavioral and neural phenotypes in these mouse models will inform the selection of affected ASD populations for future clinical assessment. Because unique patterns of visual behavioral and neurophysiological modulation are known to be indicative of dysfunction at specific sites in the corticothalamic circuit, these assessments could also reveal the locus of pathology underlying these genetically defined disorders. The use of comparable protocols across mice and humans will improve the mechanistic understanding of ASD pathogenesis and could ultimately reveal markers for accelerated ASD identification.