Neuronal Activity in the Auditory System of the Fmr1 KO Mouse

This dissertation examined how the auditory system in the Fmr1 KO mouse, amodel of Fragile X Syndrome (FXS), processes sounds as a way to examine mechanismsthat cause auditory hypersensitivity in this autism spectrum disorder. Using a molecularmarker for neuronal activity, cFos, and single unit electrophysiology recordings inresponse to auditory stimuli, we sought to understand auditory hypersensitivity in theFmr1 KO mouse. We found a difference in cFos expression between WT and Fmr1 KOmice that is both age and region specific. Single-unit recording in the inferior colliculusrevealed higher spontaneous activity, higher response magnitude, broader tuning,longer latency, greater minimum threshold, and greater response to SAM tones inneurons tuned to CF< 20 kHz in the inferior colliculus. These results suggest an overallexcitability 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 ofFXS, audiogenic seizure and conventional audiology tests (auditory brainstem response(ABR) and distortion product otoacoustic emissions (DPOAE)). Our results show acorrelation between audiogenic seizure severity and sound intensity. We did not see adifference in ABR amplitudes between genotypes; however, there was latency deficits inpeak III and V of the ABR waveform. The DPOAE reveal no difference between Fmr1 KOand WT mice in Input/Output functions of magnitude and phase. These findings suggestthat no auditory deficits can be detected with conventional audiology tests except forlatency of peak III and peak V in the ABR waveform.ixOverall, we interpret the increase in response magnitude as hyperexcitability inthe inferior colliculus that is present during development; particularly at P21, which mayexplain the increase in susceptibility to audiogenic seizure at this age. The proposedmechanism is impairments in GABAergic functions because many of the deficits wefound are in neurons with CF< 20 kHz, a region which is higher in GABA terminals than inregion with CF>= 20 kHz