Abstract
Hidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests. Animals and humans with HHL have normal auditory thresholds but defective cochlear neurotransmission, that is, reduced suprathreshold amplitude of the sound-evoked auditory nerve compound action potential. Currently, the only cellular mechanism known for HHL is loss of inner hair cell synapses (synaptopathy). Here we report that transient loss of cochlear Schwann cells results in permanent auditory deficits characteristic of HHL. This auditory neuropathy is not associated with synaptic loss, but rather with disruption of the first heminodes at the auditory nerve peripheral terminal. Thus, this study identifies a new mechanism for HHL, highlights the long-term consequences of transient Schwann cell loss on hearing and might provide insights into the causes of the auditory deficits reported in patients that recover from acute demyelinating diseases such as Guillain–Barré syndrome.
Highlights
Hidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests
Hair cells are surrounded by supporting cells, spiral ganglion neurons (SGNs) axons are myelinated by Schwann cells and spiral ganglion cell bodies are wrapped by satellite cells (Fig. 1a)
As anticipated from prior studies of mice with diphtheria toxin fragment A (DTA)-induced ablation of proteolipid protein 1 (Plp1)-expressing cells[19], tamoxifen intraperitoneal (i.p.) injection to mice carrying Plp1/CreERT transgene and Rosa26DTA alleles [DTA( þ / À ):Plp1/Cre( þ / À )] from P21 to 23 resulted in uncoordinated gait and hind-limb paralysis between 1 and 2 weeks post DTA expression followed by complete recovery of normal gait by 3–4 weeks post DTA expression
Summary
Hidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests. This auditory neuropathy is not associated with synaptic loss, but rather with disruption of the first heminodes at the auditory nerve peripheral terminal. This transient Schwann cell loss results in a permanent auditory impairment characteristic of HHL This HHL differs from that seen after noise exposure or ageing in that it occurs without alterations in synaptic density but rather correlates with a specific and permanent disruptions of the first heminodes at the auditory nerve axon close to the IHCs. the two types of HHL occur independently (noise exposures that cause HHL do not disrupt heminodes) and they are additive. These results uncover a new mechanism for the pathogenesis of HHL and a new consequence of myelin defects on the normal function of the nervous system
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