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Auditory Processing and Ultrasonic Vocalization Production in a Mouse Model of Fragile X Syndrome

  • Author(s): Rotschafer, Sarah Elizabeth
  • Advisor(s): Razak, Khaleel A.
  • et al.
Abstract

Fragile X syndrome (FXS) is the most common cause of inherited intellectual impairment and best understood single cause autism. Symptoms of FXS include social anxiety, repetitive behavior, communication disorders, hyperactivity, and seizures. Additionally, event related potential studies using sound stimuli indicate that auditory processing is abnormal in FXS. Many symptoms of FXS have been replicated in the Fmr1 knockout (KO) mice, which serve as a useful model for studying sensory processing abnormalities and symptoms associated with FXS. Fmr1 KO mice exhibit acoustic hypersensitivity and propensity for audiogenic seizures, which suggests altered auditory processing, though the nature of such changes are unknown. Although evidence of unusual social interaction and repetitive behaviors has been found in Fmr1 KO mice, communication anomalies have not yet been modeled. In order to establish the Fmr1 KO mouse as a model for the auditory processing and communication disorders associated with FXS, we developed an assay for assessing vocalization production and performed single unit extracellular electrophysiological recordings in the auditory cortex of Fmr1 KO mice. To quantify possible communication abnormalities in Fmr1 KO mice, we elicited mouse ultrasonic vocalizations (USV) by placing male mice in contact with female mice. This technique revealed that Fmr1 KO mice produce USVs at a decreased rate when compared to wild type mice. Minocycline is a tetracycline analog that has been shown to rescue some symptoms of FXS in open label human trials. Using our USV assay, we demonstrate that minocycline treatment, USV production rate was restored to wild types levels in Fmr1 KO mice. To investigate auditory processing anomalies in Fmr1 KO mice, we performed extracellular single unit recordings in the auditory cortex of anesthetized mice. Presenting single frequency tones revealed expanded frequency tuning, enhanced response magnitude, and greater variability in first spike latency. Frequency modulated sweep stimuli revealed altered sensitivity to FM sweep rate.

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