Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing

摘要: Normal hearing requires proper differentiation of afferent ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) that carry acoustic information to the brain. Within individual IHCs, presynaptic ribbons show a size gradient with larger on modiolar face smaller pillar face. This structural is associated spontaneous rates threshold sensitivity, which essential for wide dynamic range hearing. Despite their importance hearing, mechanisms direct are poorly defined. We recently identified adenomatous polyposis coli protein (APC) as key regulator interneuronal synapse maturation. Here, we APC required heterogeneity normal cochlear function. Compared wild-type littermates, conditional knock-out (cKO) mice exhibit decreased auditory brainstem responses. The IHC also perturbed. Whereas normal-developing IHCs display gradients before onset, sizes aberrant in cKOs from neonatal ages on. Reporter expression studies CaMKII-Cre used delete floxed gene present efferent olivocochlear (OC) neurons, not or SGNs. loss led increased volumes numbers OC inhibitory dopaminergic boutons SGN fibers. Our findings identify regulating heterogeneity, terminal differentiation, sensitivity. effect epithelial cell resembles nerve–muscle synapses, thereby defining global role synaptic maturation diverse types. Significance Statement study identifies novel molecules cellular interactions sensory ear,