Auditory Neuropathy after Damage to Cochlear Spiral Ganglion Neurons in Mice Resulting from Conditional Expression of Diphtheria Toxin Receptors

Auditory neuropathy (AN) is a hearing disorder characterized by normal cochlear amplification to sound but poor temporal processing and auditory perception in noisy backgrounds. These deficits likely result from impairments in auditory neural synchrony; such dyssynchrony of the neural responses has been linked to demyelination of auditory nerve fibers. However, no appropriate animal models are currently available that mimic this pathology. In this study, Cre-inducible diphtheria toxin receptor (iDTR (+/+)) mice were cross-mated with mice containing Cre (Bhlhb5-Cre (+/−)) specific to spiral ganglion neurons (SGNs). In double-positive offspring mice, the injection of diphtheria toxin (DT) led to a 30–40% rate of death for SGNs, but no hair cell damage. Demyelination types of pathologies were observed around the surviving SGNs and their fibers, many of which were distorted in shape. Correspondingly, a significant reduction in response synchrony to amplitude modulation was observed in this group of animals compared to the controls, which had a Cre(−) genotype. Taken together, our results suggest that SGN damage following the injection of DT in mice with Bhlhb5-Cre (+/−) and iDTR (+/−) is likely to be a good AN model of demyelination.