Abstract
The auditory brainstem compares sound-evoked excitation and inhibition from both ears to compute sound source location and determine spatial acuity. 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 spatial acuity deficits in FXS. To test the hypothesis that FXS-related alterations to brainstem circuits impair spatial hearing abilities, a reflexive prepulse inhibition (PPI) task, with variations in sound (gap, location, masking) as the prepulse stimulus, was used on Fmr1 knockout mice and B6 controls. 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. This study further supports data in humans with FXS that show similar deficits in PPI.
Significance Statement: This is the first study to characterize auditory spatial acuity in a mouse model of FXS. We saw minor differences in Fmr1 mice compared to B6 mice in several measures of auditory acuity as measured by inhibition of the startle response. Fmr1 mice had increased latency to startle for almost all conditions compared to B6 mice suggesting altered timing to acoustic cues. These experiments further show that, consistent with patient report and anatomical/physiological data, the auditory system is altered in a mouse model of FXS, though with some potential compensation leading to a subtle behavioral impact.
Footnotes
The authors declare no competing financial interests.
Supported in part by NIH R01 DC017924 (Klug). Dr. McCullagh was funded by FRAXA and NIH 3T32DC012280-05S1.
Elizabeth A. McCullagh and Shani Poleg co-first authors.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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