Mechanisms underlying auditory processing deficits in Fragile X syndrome

Elizabeth A. McCullagh, Sarah E. Rotschafer, Benjamin D. Auerbach, Achim Klug, Leonard K. Kaczmarek, Karina S. Cramer, Randy J. Kulesza, Khaleel A. Razak, Jonathan W. Lovelace, Yong Lu, Ursula Koch, Yuan Wang

Research output: Contribution to journalReview articlepeer-review


Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.

Original languageEnglish (US)
Pages (from-to)3501-3518
Number of pages18
JournalFASEB Journal
Issue number3
StatePublished - Mar 1 2020
Externally publishedYes


  • Fragile X syndrome
  • auditory system
  • autism spectrum disorders
  • circuit development
  • hyperacusis
  • synaptic transmission

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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