Auditory binaural and spatial hearing impairments in a Fragile X Syndrome mouse model

The auditory brainstem compares sound-evoked excitation and inhibition from both ears to compute sound source location. Although alterations to the anatomy and physiology of the auditory brainstem have been demonstrated in Fragile X Syndrome (FXS) it is not known whether these changes cause sound localization impairments in FXS. To test the hypothesis that FXS-related alterations to brainstem circuits impair spatial hearing abilities, a reflexive prepulse inhibition (PPI) task, with sound source location as the prepulse stimulus, was used to show that Fmr1 knockout mice have decreased inhibition of their startle responses. Specifically, Fmr1 mice show decreased PPI compared to wildtype during gap detection, changes in sound source location, and spatial release from masking with no alteration to their overall startle thresholds compared to wildtype. Lastly, Fmr1 mice have increased latency to respond in these tasks suggesting additional impairments in the pathway responsible for reacting to a startling sound.