Sound Exposure and c-Fos Expression in the Cochlear Nucleus of Fmr1-Knockout Mice

Fragile X Syndrome (FXS) is a genetic disorder that affects 1 in 4,000 males and 1 in 6,000 females in the United States.¹ It is caused by a trinucleotide repeat expansion in the Fmr1 gene that leads to a loss of the protein product FMRP. Although several studies have shown that individuals with FXS exhibit auditory hypersensitivity, the relationship between sound exposure and neuronal activity remains sparsely examined.² Here, we explore the neuronal activity of Fmr1-knockout (KO) mice by exposing them to varying sound levels and quantifying the resulting c-Fos expression found in mice cochlear nuclei. 14-day-old (P14) Fmr1-KO mice were distributed into four experimental groups. Each group was exposed to 88, 70, 65 and 60 dB of sound for approximately two hours. Following exposure to sound, mice were perfused and their brains were harvested. Neuronal activity was quantified in the cochlear nucleus (CN) using c-Fos immunostaining. c-Fos is an immediate early marker known to be activated in response to neuronal activity. An analysis of the data revealed that c-Fos expression in Fmr1-KO mice is sound pressure level-dependent; Fmr1-KO mice exposed to the highest sound level showed the most c-Fos expression while Fmr1-KO mice exposed to the lowest sound level exhibited the least c-Fos expression. These findings show that auditory stimulation does lead to c-Fos expression in the cochlear nucleus of Fmr1 KO mice and this occurs in a dose-dependent manner. Although we were unable to apply these experiments to wild-type mice, we anticipate that the c-Fos immunoreactivity will be different between mutant and nonmutant groups and plan to compare these in the future.