Altered auditory processing in a mouse model of fragile X syndrome

Brain Res. 2013 Apr 19:1506:12-24. doi: 10.1016/j.brainres.2013.02.038. Epub 2013 Feb 28.


This study provides the first description of auditory cortical processing in a mouse model of Fragile X Syndrome (FXS). FXS is a genetic cause of intellectual impairment and is an autism spectrum disorder. Human studies with auditory evoked potentials indicate that FXS is associated with abnormal auditory processing. The Fmr1 knock-out (KO) mouse is a useful model for studying FXS. The KO mice show acoustic hypersensitivity and propensity for audiogenic seizures, suggesting altered auditory responses. However, the nature of changes at the neuronal level is not known. Here we conducted in vivo single unit extracellular electrophysiology in the auditory cortex of urethane/xylazine-anesthetized Fmr1 KO mice in response to tones and frequency modulated (FM) sweeps. Using tones as stimuli, we report expanded frequency tuning, enhanced response magnitude, and more variable first spike latencies in Fmr1 KO mice compared to wild-type controls. FM sweep stimuli revealed altered sensitivity to the rate of frequency change indicating abnormal spectrotemporal processing. There was no difference in FM sweep direction selectivity. Consistent with studies of the somatosensory cortex, these data point to hyper-responsiveness of auditory neurons as a key processing abnormality in FXS. Auditory neural responses can serve as outcome measures in preclinical trials of therapeutics for FXS as well as serve as physiological probes to study their mechanisms of action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Cortex / physiopathology*
  • Auditory Perception / physiology*
  • Disease Models, Animal
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Single-Cell Analysis


  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein