Tinnitus development is associated with synaptopathy of inner hair cells in Mongolian gerbils

AbstractHuman hearing loss (HL) is often accompanied by comorbidities like tinnitus which is affecting up to 15% of the adult population. Rodent animal studies could show that tinnitus may not only be a result of apparent HL due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells (IHC) already induced by moderate sound traumata. Here we investigate synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus. Tinnitus was induced by a mild monaural acoustic trauma leading to monaural noise induced HL in the animals, quantified by auditory brainstem response (ABR) audiometry. Behavioral signs of tinnitus percepts were detected by measurement of prepulse inhibition of the acoustic startle response in a gap-noise paradigm. 14 days after trauma, the cochleae of both ears were isolated and IHC synapses were counted within several spectral regions of the cochlea. Behavioral signs of tinnitus were only found in animals with IHC synaptopathy, independent of type of HL. On the other hand, animals with apparent HL but without behavioral signs of tinnitus showed a reduction in amplitudes of ABR waves I&II but no significant changes in the number of synapses at the IHC. We conclude – in line with the literature – that HL is caused by damage to the IHC or by other reasons but that the development of tinnitus, at least in our animal model, is closely linked to synaptopathy at the IHC.

Download Full-text

Faculty Opinions recommendation of Inner hair cells are not required for survival of spiral ganglion neurons in the adult cochlea.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13483964.14861062 ◽

2012 ◽

Author(s):

Andy Groves

Keyword(s):

Hair Cells ◽

Spiral Ganglion ◽

Spiral Ganglion Neurons ◽

Inner Hair Cells ◽

Ganglion Neurons

Download Full-text

Faculty Opinions recommendation of LRRC52 regulates BK channel function and localization in mouse cochlear inner hair cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736503545.793580199 ◽

2020 ◽

Author(s):

Tobias Moser

Keyword(s):

Hair Cells ◽

Bk Channel ◽

Inner Hair Cells ◽

Channel Function

Download Full-text

Inner hair cell stereocilia are embedded in the tectorial membrane

Nature Communications ◽

10.1038/s41467-021-22870-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Pierre Hakizimana ◽

Anders Fridberger

Keyword(s):

Electron Microscopy ◽

Hair Cell ◽

Mechanical Stimulation ◽

Hair Cells ◽

Viscous Drag ◽

Tectorial Membrane ◽

Inner Hair Cell ◽

Inner Hair Cells ◽

Inward Currents

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.

Download Full-text

The efferents interconnecting auditory inner hair cells

Hearing Research ◽

10.1016/0378-5955(94)90059-0 ◽

1994 ◽

Vol 75 (1-2) ◽

pp. 81-92 ◽

Cited By ~ 19

Author(s):

H.M. Sobkowicz ◽

S.M. Slapnick

Keyword(s):

Hair Cells ◽

Inner Hair Cells

Download Full-text

Calcium- and Calmodulin-Dependent Inactivation of Calcium Channels in Inner Hair Cells of the Rat Cochlea

Journal of Neurophysiology ◽

10.1152/jn.01174.2007 ◽

2008 ◽

Vol 99 (5) ◽

pp. 2183-2193 ◽

Cited By ~ 34

Author(s):

Lisa Grant ◽

Paul Fuchs

Keyword(s):

Calcium Channels ◽

Hair Cells ◽

Calcium Currents ◽

Resting Potential ◽

Resting Membrane Potential ◽

Inner Hair Cells ◽

Voltage Gated ◽

Voltage Gated Calcium Channels ◽

Dependent Inactivation ◽

Calcium Buffering

Modulation of voltage-gated calcium channels was studied in inner hair cells (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti. Whole cell voltage clamp in the presence of potassium channel blockers showed inward calcium currents with millisecond activation and deactivation kinetics. When temperature was raised from 22 to 37°C, the calcium currents of immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and developed more pronounced inactivation. This was determined to be calcium-dependent inactivation (CDI) on the basis of its reliance on external calcium (substitution with barium), sensitivity to internal calcium-buffering, and voltage dependence (reflecting the calcium driving force). After the onset of hearing at P12, IHC calcium current amplitude and the extent of inactivation were greatly reduced. Although smaller than in prehearing IHCs, CDI remained significant in the mature IHC near the resting membrane potential. CDI in mature IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo-hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of calcium buffering mechanisms and may be regulated by calmodulin-specific processes. CDI provides a means for the rate of spontaneous transmitter release to be adjusted to variations in hair cell resting potential and steady state calcium influx.

Download Full-text