Autism spectrum disorders (ASDs) are genetically heterogeneous, but whether they share a common neural-circuit-processing defect is unclear. One hypothesis is that the ratio of excitation to inhibition (the E/I ratio) in the brain’s cerebral cortex is elevated in ASDs. Elevations in this ratio could cause hyperexcitability of neural circuits, leading to impaired information processing and hypersensitivity to sensory stimuli, features commonly seen in individuals with ASD.

Daniel Feldman and his colleagues at the University of California, Berkeley will quantitatively measure neural circuit function across multiple transgenic mouse models of autism to test whether changes in E/I ratio or other common modes of circuit dysfunction occur. In preliminary studies supported by a SFARI Explorer Award, Feldman and his team examined mice lacking FMR1 and CNTNAP2. Here, the researchers propose to extend this approach to seven different mouse models of syndromic and non-syndromic autism in an effort to test whether common motifs of circuit dysfunction occur.

Feldman and his team will use neurophysiological and behavioral methods to measure E/I ratio, circuit excitability, sensory processing and sensory perception. They will focus on the primary somatosensory cortex, where circuit function is well understood. Processing disorders in this area may relate to tactile hypersensitivity, which is common in individuals with ASD.

If shared circuit defects exist, this would argue for a search for broadly effective therapies that restore circuit function across multiple forms of ASD. The methods developed here could be applied to efficiently screen for therapeutic approaches that restore circuit function and ameliorate sensory abnormalities in individuals with ASD.