Neuronal Activity in the Auditory System of the Fmr1 KO Mouse
- Author(s): Nguyen, Anna
- Advisor(s): Abdulrazak, Khaleel R.
- et al.
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.
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.