A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics

Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30A88V/A88V mice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30A88V/A88V compared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea. Surprisingly, the endocochlear potential that drives mechanoelectrical transduction currents in outer hair cells and hence cochlear amplification is greatly reduced in CD-1Cx30A88V/A88V mice. Yet, the saturating amplitudes of cochlear microphonic potentials in CD-1Cx30A88V/A88V and CBA/J mice are comparable. Although not conclusive, these results are compatible with the proposal that transmembrane potentials, determined mainly by extracellular potentials, drive somatic electromotility of outer hair cells

Les romans sur Rocambole de Ponson du Terrail comme source d’inspiration pour une bande d’escrocs moscovites du xixe siècle

L’article étudie la réception sociale et littéraire des romans sur Rocambole de Ponson du Terrail (1829-1871) en Russie de la fin du xixe siècle. Vers 1871, une bande d’escrocs, nommée « Valets de cœur », fut créée à Moscou. On retrouve ce nom dans le titre d’un épisode du cycle Rocambole: « Le Club des valets de cœur », publié en 1858 (La Patrie). Ce n’est pas une coïncidence : les jeunes escrocs reproduisaient les crimes des personnages littéraires dans la vie réelle. L’affaire des « Valets de cœur » donna lieu à un grand procès et fut suivie par les écrivains russes de l’époque qui s’interrogeaient sur l’avenir du pays. Ils ont considéré ce phénomène comme un indicateur social d’une Russie perdant sa stabilité.The article studies the social and literary reception of the Rocambolesque novels of Ponson du Terrail (1829-1871) in Russia at the end of the nineteenth century. Around 1871, a gang of con men named « Valets de Cœur » was created in Moscow. The same name can be found in the Rocambole cycle: “Le Club des valets de cœur” – published in 1858 (La Patrie). It is not a coincidence: the young con men reproduced exactly and in reality the crimes that were commited by the book’s characters. The case of the « Valets de cœur » culminated in a great legal trial and drew particular attention from the Russian writers of the time — who questioned the future of the country. They considered the phenomenon as a social signpost of a Russia nation that was losing its stability

A tectorin-based matrix and planar-cell-polarity genes are required for normal collagen-fibril orientation in the developing tectorial membrane

The tectorial membrane is an extracellular structure of the cochlea. It develops on the surface of an epithelium and contains collagen fibrils embedded in a tectorin-based matrix. The collagen fibrils are oriented radially with an apically-directed slant - a feature considered critical for hearing. To determine how this pattern is generated, collagen-fibril formation was examined in mice lacking a tectorin-based matrix, epithelial cilia, or the planar-cell-polarity genes Vangl2 and Ptk7. In wild-type mice, collagen-fibril bundles appear within a tectorin-based matrix at E15.5 and, as fibril-number rapidly increases, become co-aligned and correctly oriented. Epithelial-width measurements and data from Kif3acKO mice suggest, respectively, radial stretch and cilia play little, if any, role in determining normal collagen-fibril orientation, but evidence from tectorin-knockout mice indicates confinement is important. PRICKLE2 distribution reveals the planar-cell-polarity axis in the underlying epithelium is organised along the length of the cochlea and, in mice in which this polarity is disrupted, the apically-directed collagen offset is no longer observed. These results highlight the importance of the tectorin-based matrix and epithelial signals for precise collagen organisation in the tectorial membran

Amplification mode differs along the length of the mouse cochlea as revealed by connexin 26 deletion from specific gap junctions

The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forcesdelivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters’ cells (DCs) and pillar cells (PCs), coupled by gap- junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock- out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving- voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses. However, the Cx26 cKO desensitizes mid-high-frequency DPOAEs and active BM responses and sensitizes low-mid-frequency neural excitation. This functional segregation may indicate that the flexible, apical turn cochlear partition facilitates transfer of OHC displacements (isotonic forces) for cochlear amplification and neural excitation. DC and PC Cx26 expression is essential for cochlear amplification in the stiff basal turn, possibly through maintaining cochlear partitionmechanical impedance, thereby ensuring effective transfer of OHC isometric forces

A Comparison of Distortion Product Otoacoustic Emission Properties in Meniere's Disease Patients and Normal-Hearing Participants

Objectives: Postmortem examination of temporal bones of Meniere's disease patients consistently show dilated endolymphatic spaces of the inner ear, for which the term endolymphatic hydrops has been coined. During the past decade, magnetic resonance imaging techniques for the inner ear appeared, advancing the diagnosis of Meniere's disease. They require, however, a field-strength of at least 3 T, are costly and not universally available. Alternative, noninvasive, cost-effective tests with high sensitivity and specifity for endolymphatic hydrops are desirable. In this study, we test the suitability of distortion product otoacoustic emissions (DPOAEs) for endolymphatic hydrops detection. Previous measurements of the commonly recorded cubic DPOAEs mainly register cochlear hearing loss and are not specific for Meniere's disease. Simultaneous recordings of cubic and quadratic DPOAEs might be more suitable to detect endolymphatic hydrops, because both DPOAE orders react differently to changes of the cochlear operating point as they might occur in Meniere's disease patients. Design: Cubic and quadratic DPOAEs were recorded in normal-hearing participants (N = 45) and in the affected and unaffected ears of patients with a diagnosis of definite Meniere's disease (N = 32). First, to assess the integrity of DPOAE-generating mechanisms, cubic DPOAE-grams were obtained with primary tone frequencies f(2) between 1 and 8 kHz with primary tone levels l(1) = 60 dB SPL and l(2) = 50 dB SPL, and a fixed primary tone frequency ratio of 1.22. Then, cubic and quadratic DPOAEs were simultaneously recorded with primary tone levels l(1) = l(2) = 65 dB SPL and at primary tone frequencies f(2) = 4 and 5 kHz, where f(1) was successively varied such that the ratio f(2)/f(1) ranged between 1.1 and 1.6 in 0.04 steps while quadratic and cubic DPOAE levels were extracted from the same recording. Results: Cubic DPOAEs were significantly reduced in the affected ears of Meniere's disease patients, and slightly reduced in the unaffected ears of Meniere's disease patients, relative to the ears of normal-hearing participants. In contrast, no significant changes could be seen in quadratic DPOAEs across the ears of normal-hearing participants and Meniere's disease patients. Conclusions: We could identify a relatively good preservation of quadratic DPOAE levels in relation to a reduction of cubic DPOAE levels as a potential noninvasive diagnostic approach in the early stage of suspected Meniere's disease. Future studies validating the differential diagnostic power of this parameter in control groups with nonhydropic forms of hearing loss are warranted

Emilin 2 promotes the mechanical gradient of the cochlear basilar membrane and resolution of frequencies in sound

The detection of different frequencies in sound is accomplished with remarkable precision by the basilar membrane (BM), an elastic, ribbon-like structure with graded stiffness along the cochlear spiral. Sound stimulates a wave of displacement along the BM with maximal magnitude at precise, frequency-specific locations to excite neural signals that carry frequency information to the brain. Perceptual frequency discrimination requires fine resolution of this frequency map, but little is known of the intrinsic molecular features that demarcate the place of response on the BM. To investigate the role of BM microarchitecture in frequency discrimination, we deleted extracellular matrix protein emilin 2, which disturbed the filamentous organization in the BM. Emilin2-/- mice displayed broadened mechanical and neural frequency tuning with multiple response peaks that are shifted to lower frequencies than normal. Thus, emilin 2 confers a stiffness gradient on the BM that is critical for accurate frequency resolution