UC Riverside

Background

Fragile X syndrome (FXS) is the most common genetic cause of autism and intellectual disability. Fragile X mental retardation gene (Fmr1) knock-out (KO) mice display core deficits of FXS, including abnormally increased sound-evoked responses, and show a delayed development of parvalbumin (PV) cells. Here, we present the surprising result that sound exposure during early development reduces correlates of auditory hypersensitivity in Fmr1 KO mice.

Methods

Fmr1 KO and wild-type (WT) mice were raised in a sound-attenuated environment (AE) or sound-exposed (SE) to 14 kHz tones (5 Hz repetition rate) from P9 until P21. At P21-P23, event-related potentials (ERPs), dendritic spine density, PV expression and phosphorylation of tropomyosin receptor kinase B (TrkB) were analyzed in the auditory cortex of AE and SE mice.

Results

Enhanced N1 amplitude of ERPs, impaired PV cell development, and increased spine density in layers (L) 2/3 and L5/6 excitatory neurons were observed in AE Fmr1 KO compared to WT mice. In contrast, developmental sound exposure normalized ERP N1 amplitude, density of PV cells and dendritic spines in SE Fmr1 KO mice. Finally, TrkB phosphorylation was reduced in AE Fmr1 KO, but was enhanced in SE Fmr1 KO mice, suggesting that BDNF-TrkB signaling may be regulated by sound exposure to influence PV cell development.

Conclusions

Our results demonstrate that sound exposure, but not attenuation, during early developmental window restores molecular, cellular and functional properties in the auditory cortex of Fmr1 KO mice, and suggest this approach as a potential treatment for sensory phenotypes in FXS.