Beneficial effects of sound exposure on auditory cortex development in a mouse model of Fragile X Syndrome

Anna O Kulinich; Sarah M Reinhard; Maham Rais; Jonathan W Lovelace; Veronica Scott; Devin K Binder; Khaleel A Razak; Iryna M Ethell

doi:10.1016/j.nbd.2019.104622

Beneficial effects of sound exposure on auditory cortex development in a mouse model of Fragile X Syndrome

Neurobiol Dis. 2020 Feb:134:104622. doi: 10.1016/j.nbd.2019.104622. Epub 2019 Nov 5.

Authors

Anna O Kulinich¹, Sarah M Reinhard², Maham Rais³, Jonathan W Lovelace², Veronica Scott¹, Devin K Binder⁴, Khaleel A Razak⁵, Iryna M Ethell⁶

Affiliations

¹ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
² Psychology Department, University of California, Riverside, CA, USA.
³ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA; Biomedical Sciences Graduate Program, University of California, Riverside, CA, USA.
⁴ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA; Neuroscience Graduate Program, University of California, Riverside, CA, USA; Biomedical Sciences Graduate Program, University of California, Riverside, CA, USA.
⁵ Psychology Department, University of California, Riverside, CA, USA; Neuroscience Graduate Program, University of California, Riverside, CA, USA; Biomedical Sciences Graduate Program, University of California, Riverside, CA, USA. Electronic address: Khaleel@ucr.edu.
⁶ Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA; Neuroscience Graduate Program, University of California, Riverside, CA, USA; Biomedical Sciences Graduate Program, University of California, Riverside, CA, USA. Electronic address: iryna.ethell@medsch.ucr.edu.

PMID: 31698054
DOI: 10.1016/j.nbd.2019.104622

Abstract

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.

Keywords: Auditory cortex; Autism; Fragile X Syndrome; Parvalbumin interneurons; Perineuronal nets; Sensory hypersensitivity.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acoustic Stimulation*
Animals
Auditory Cortex / physiopathology*
Disease Models, Animal
Evoked Potentials / physiology
Fragile X Syndrome / physiopathology*
Male
Mice
Mice, Knockout
Neurogenesis*