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  • Sensory transduction is required for normal development and maturation of cochlear inner hair cell synapses.

Sensory transduction is required for normal development and maturation of cochlear inner hair cell synapses.

eLife (2021-11-05)
John Lee, Kosuke Kawai, Jeffrey R Holt, Gwenaëlle Sg Géléoc
ABSTRACT

Acoustic overexposure and aging can damage auditory synapses in the inner ear by a process known as synaptopathy. These insults may also damage hair bundles and the sensory transduction apparatus in auditory hair cells. However, a connection between sensory transduction and synaptopathy has not been established. To evaluate potential contributions of sensory transduction to synapse formation and development, we assessed inner hair cell synapses in several genetic models of dysfunctional sensory transduction, including mice lacking transmembrane channel-like (Tmc) 1, Tmc2, or both, in Beethoven mice which carry a dominant Tmc1 mutation and in Spinner mice which carry a recessive mutation in transmembrane inner ear (Tmie). Our analyses reveal loss of synapses in the absence of sensory transduction and preservation of synapses in Tmc1-null mice following restoration of sensory transduction via Tmc1 gene therapy. These results provide insight into the requirement of sensory transduction for hair cell synapse development and maturation.

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Anti-GluR2 Antibody, clone 14C12.2, clone 14C12.2, from mouse