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Two-tone distortion in reticular lamina vibration of the living cochlea.

ABSTRACT: It has been demonstrated that isolated auditory sensory cells, outer hair cells, can generate distortion products at low frequencies. It remains unknown, however, whether or not motile outer hair cells are able to generate two-tone distortion at high frequencies in living cochleae under the mechanical loads caused by surounding tissues and fluids. By measuring sub-nanometer vibration directly from the apical ends of outer hair cells using a custom-built heterodyne low-coherence interferometer, here we show outer hair cell-generated two-tone distortion in reticular lamina motion in the living cochlea. Reticular-lamina distortion is significantly greater and occurs at a broader frequency range than that of the basilar membrane. Contrary to expectations, our results indicate that motile outer hair cells are capable of generating two-tone distortion in vivo not only at the locations tuned to primary tones but also at a broad region basal to these locations.

SUBMITTER: Ren T

PROVIDER: S-EPMC6972885 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Two-tone distortion in reticular lamina vibration of the living cochlea.

Ren Tianying T He Wenxuan W

Communications biology 20200121 1

It has been demonstrated that isolated auditory sensory cells, outer hair cells, can generate distortion products at low frequencies. It remains unknown, however, whether or not motile outer hair cells are able to generate two-tone distortion at high frequencies in living cochleae under the mechanical loads caused by surounding tissues and fluids. By measuring sub-nanometer vibration directly from the apical ends of outer hair cells using a custom-built heterodyne low-coherence interferometer, h ...[more]

PMID: 31965040

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Project description:Background and purposeWe sought to demonstrate that tumor necrosis factor (TNF)-α, via sphingosine-1-phosphate signaling, has the potential to alter cochlear blood flow and thus, cause ischemic hearing loss.MethodsWe performed intravital fluorescence microscopy to measure blood flow and capillary diameter in anesthetized guinea pigs. To measure capillary diameter ex vivo, capillary beds from the gerbil spiral ligament were isolated from the cochlear lateral wall and maintained in an organ bath. Isolated gerbil spiral modiolar arteries, maintained and transfected in organ culture, were used to measure calcium sensitivity (calcium-tone relationship). In a clinical study, a total of 12 adult patients presenting with typical symptoms of sudden hearing loss who were not responsive or only partially responsive to prednisolone treatment were identified and selected for etanercept treatment. Etanercept (25 mg s.c.) was self-administered twice a week for 12 weeks.ResultsTNF-α induced a proconstrictive state throughout the cochlear microvasculature, which reduced capillary diameter and cochlear blood flow in vivo. In vitro isolated preparations of the spiral modiolar artery and spiral ligament capillaries confirmed these observations. Antagonizing sphingosine-1-phosphate receptor 2 subtype signaling (by 1 μmol/L JTE013) attenuated the effects of TNF-α in all models. TNF-α activated sphingosine kinase 1 (Sk1) and induced its translocation to the smooth muscle cell membrane. Expression of a dominant-negative Sk1 mutant (Sk1(G82D)) eliminated both baseline spiral modiolar artery calcium sensitivity and TNF-α effects, whereas a nonphosphorylatable Sk1 mutant (Sk1(S225A)) blocked the effects of TNF-α only. A small group of etanercept-treated, hearing loss patients recovered according to a 1-phase exponential decay (half-life=1.56 ± 0.20 weeks), which matched the kinetics predicted for a vascular origin.ConclusionsTNF-α indeed reduces cochlear blood flow via activation of vascular sphingosine-1-phosphate signaling. This integrates hearing loss into the family of ischemic microvascular pathologies, with implications for risk stratification, diagnosis, and treatment.

Dataset Information

Two-tone distortion in reticular lamina vibration of the living cochlea.

Publications

Two-tone distortion in reticular lamina vibration of the living cochlea.

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