UC Riverside

This dissertation examined how the auditory system in the Fmr1 KO mouse, a

model of Fragile X Syndrome (FXS), processes sounds as a way to examine mechanisms

that cause auditory hypersensitivity in this autism spectrum disorder. Using a molecular

marker for neuronal activity, cFos, and single unit electrophysiology recordings in

response to auditory stimuli, we sought to understand auditory hypersensitivity in the

Fmr1 KO mouse. We found a difference in cFos expression between WT and Fmr1 KO

mice that is both age and region specific. Single-unit recording in the inferior colliculus

revealed higher spontaneous activity, higher response magnitude, broader tuning,

longer latency, greater minimum threshold, and greater response to SAM tones in

neurons tuned to CF< 20 kHz in the inferior colliculus. These results suggest an overall

excitability or lack of inhibition in the inferior colliculus of the mouse model for FXS.

In addition, this dissertation describes two areas in the auditory processing of

FXS, audiogenic seizure and conventional audiology tests (auditory brainstem response

(ABR) and distortion product otoacoustic emissions (DPOAE)). Our results show a

correlation between audiogenic seizure severity and sound intensity. We did not see a

difference in ABR amplitudes between genotypes; however, there was latency deficits in

peak III and V of the ABR waveform. The DPOAE reveal no difference between Fmr1 KO

and WT mice in Input/Output functions of magnitude and phase. These findings suggest

that no auditory deficits can be detected with conventional audiology tests except for

latency of peak III and peak V in the ABR waveform.

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Overall, we interpret the increase in response magnitude as hyperexcitability in

the inferior colliculus that is present during development; particularly at P21, which may

explain the increase in susceptibility to audiogenic seizure at this age. The proposed

mechanism is impairments in GABAergic functions because many of the deficits we

found are in neurons with CF< 20 kHz, a region which is higher in GABA terminals than in

region with CF>= 20 kHz.