Sensory transduction is required for development of hair cell synapses

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.