Foxg1 gene mutation impairs auditory cortex response and reduces sound tolerance.

FOXG1 syndrome (FS) is a rare and devastating neurodevelopmental disorder affected by FOXG1 gene mutations and reduced sound tolerance has been reported in children with FS. Effects of single missense mutation of Foxg1 gene on auditory function and behavior were studied using the G216S mouse model. G216S mice showed significantly reduced gap-induced prepulse inhibition, suggesting poor temporal processing without hearing loss. Increased running and freezing behaviors under loud sounds were also found in G216 mice, suggesting aversive sound behaviors. Electrophysiological assessment of the auditory cortex of G216 mice revealed a slightly reduced amplitude and enlarged poststimulus responses to the sound stimulus. The layer function analysis using current source density revealed reduced layer-specific response in the G216S mice. Immunocytochemistry found Foxg1 gene mutation affects cortical layer differentiations and reduced cortical neurons, which are consistent with the physiological results. Our study suggests that the Foxg1 mutation impaired cortical development. The results are consistent with other models of autism spectrum disorders (ASDs), suggesting that the G216S mouse model may represent a hyperacusis model of ASD. Our results provide direct evidence that a single-nucleotide mutation of the Foxg1 gene can affect cortical layer development and auditory processing and reduce sound tolerance.