Delayed development of inner hair cell ribbon synapses in a mouse model of fragile X syndrome

Abstract

Clinical features of FXS phenotype include intellectual disability, repetitive behaviors, social communication deficit and also commonly manifested auditory hypersensitivity for acoustic stimuli. The electrophysiological studies have shown that FXS patients and Fmr1 KO mice display improper processing of auditory information in the cortical areas of the brain and the spiral ganglion of cochlea. Synapses formed by spiral ganglion neurons on sensory hair cells (HC) are the first connection on the path that conveys the auditory information from the sensory cells to the brain. We confirmed the presence of fragile X messenger ribonucleoprotein (FMRP) in the inner hair cells of the cochlea. Next, we analyzed the morphology of IHC ribbon synapses in early stages of postnatal development (P5, P14) and detected their delayed developmental maturation in Fmr1 KO mice. Interestingly the ultrastructure of inner hair cell ribbon synapses studied by electron microscopy in the adult mice have shown no specific dysmorphologies. Delayed maturation of presynaptic ribbons of auditory hair cells in Fmr1 KO mice may contribute to abnormal development of circuits induced by auditory experience.