Firing Property of Inferior Colliculus Neurons Affected by FMR1 Gene Mutation

Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syndrome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the normal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound (hyperacusis). The molecular basis of fragile X syndrome is thoroughly understood; however, the neural mechanisms underlying hyperacusis have not yet been determined. As the inferior colliculus (IC) is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction observed within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.