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The high sensitivity and effective frequency discrimination of sound detection performed by the auditory system rely on the dynamics of a system of hair cells. In the inner ear, these acoustic receptors are primarily attached to an overlying structure that provides mechanical coupling between the hair bundles. Although the dynamics of individual hair bundles has been extensively investigated, the influence of mechanical coupling on the motility of the system of bundles remains underdetermined. We developed a technique of mechanically coupling two active hair bundles, enabling us to probe the dynamics of the coupled system experimentally. We demonstrated that the coupling could enhance the coherence of hair bundles' spontaneous oscillation, as well as their phase-locked response to sinusoidal stimuli, at the calcium concentration in the surrounding fluid near the physiological level. The empirical data were consistent with numerical results from a model of two coupled nonisochronous oscillators, each displaying a supercritical Hopf bifurcation. The model revealed that a weak coupling can poise the system of unstable oscillators closer to the bifurcation by a shift in the critical point. In addition, the dynamics of strongly coupled oscillators far from criticality suggested that individual hair bundles may be regarded as nonisochronous oscillators. An optimal degree of nonisochronicity was required for the observed tuning behavior in the coherence of autonomous motion of the coupled system.
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http://dx.doi.org/10.1016/j.bpj.2020.11.2273 | DOI Listing |
Adv Sci (Weinh)
September 2025
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Palo Alto, 94304, USA.
The plasma membrane is actively regulated by lipid transporters that create electrochemical gradients between leaflets, and passively by scramblases that dissipate these gradients. Membrane properties such as lipid packing are critical for the proper function of transmembrane proteins, particularly mechanosensitive ion channels. Mechanosensation is a key component of many sensory processes including balance, and hearing.
View Article and Find Full Text PDFNeurobiol Aging
August 2025
Molecular and Integrative Biosciences Research Programme, University of Helsinki, Helsinki 00010, Finland. Electronic address:
Hallmarks of sensorineural hearing loss are elevated hearing thresholds and defects in temporal auditory processing, the former being often caused by outer hair cell (OHC) damage, and the latter by the loss of synapses between inner hair cells (IHCs) and spiral ganglion neurons. In the well-studied CBA/CaJ mouse strain, these impairments are disconnected, IHC synaptopathy preceding OHC loss. We have investigated the relationship between IHC synaptopathy and OHC loss in the C57BL/6J (B6) and ICR mouse strains that model accelerated age-related hearing loss.
View Article and Find Full Text PDFNeurosci Bull
August 2025
ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200031, China.
Vestibular hair cells (HCs) in the inner ear, crucial for balance and spatial orientation, are classified into type I and type II subtypes, but the mechanisms regulating their differentiation remain unclear. In this study, we examined the role of Pou4f3, an important transcription factor, in vestibular HC differentiation using Pou4f3 (deficient) and Pou4f3 (knockout) mouse models. In Pou4f3-deficient mice, the HC number decreased, and immature HCs failed to develop type I characteristics, indicating a developmental arrest.
View Article and Find Full Text PDFmedRxiv
August 2025
Mass Eye and Ear, Eaton Peabody Laboratories, Boston, MA, 02114, USA.
Identifying new genes responsible for non-syndromic hearing loss remains a critical goal, as many individuals with hereditary deafness still lack a molecular diagnosis despite comprehensive genetic testing. The tectorial membrane (TM) is a specialized, collagen-rich, acellular matrix of the inner ear, essential for stimulating mechanosensitive hair cell bundles during sound transduction, and its structural integrity is critical for frequency tuning and auditory sensitivity. Although mutations in genes encoding a number of non-collagenous proteins found in the TM (TECTA, CEACAM16, OTOG, OTOGL) have been identified as deafness genes, definitive evidence implicating β-tectorin (TECTB) in human hearing loss has been lacking.
View Article and Find Full Text PDFDis Model Mech
August 2025
Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Methionine sulfoxide reductases (MSRs) are enzymes responsible for catalyzing the reduction of methionine sulfoxides. We previously demonstrated that variants in human MSRB3, an MSR family member, are associated with profound autosomal recessive prelingual non-syndromic deafness, DFNB74. To better understand the role of MSRB3 in the auditory pathway, we generated complete Msrb3 gene knockout mice.
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