Enhanced cross-modal activation of sensory cortex in mouse models of autism

Synesthesia is a condition wherein one sense is evoked by another. Recent studies suggested a higher incidence of synesthesia among people with autism. However, the underlying circuit mechanism of the comorbidity remains unknown partly due to lack of animal models. Here, we measured auditory response of primary visual cortex (V1) in mouse models to estimate the mixture level of their senses. We found that the V1 auditory response exhibits bidirectional cross-modal plasticity and depends on the level of GABA-mediated inhibition. Analysis of the V1 auditory response in autistic BTBR strain revealed its contralateral bias as in primary auditory cortex, and the auditory evoked field potential was enhanced at gamma range. Furthermore, early sound-driven spike modulation of V1 was commonly shifted toward enhancement in three different autism models (BTBR, NL3 R451C, SCN1A R1407X). Disruption of excitatory/inhibitory (E/I) circuit balance is prevalent among autistic people and mouse models. Thus, our results suggest that E/I imbalance may be the common circuit dysfunction for both autism and synesthesia.