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Proceedings of the National Academy of... Jun 2023Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. As a result, the...
Functional molecular characterization of the cochlea has mainly been driven by the deciphering of the genetic architecture of sensorineural deafness. As a result, the search for curative treatments, which are sorely lacking in the hearing field, has become a potentially achievable objective, particularly cochlear gene and cell therapies. To this end, a complete inventory of cochlear cell types, with an in-depth characterization of their gene expression profiles right up to their final differentiation, is indispensable. We therefore generated a single-cell transcriptomic atlas of the mouse cochlea based on an analysis of more than 120,000 cells on postnatal day 8 (P8), during the prehearing period, P12, corresponding to hearing onset, and P20, when cochlear maturation is almost complete. By combining whole-cell and nuclear transcript analyses with extensive in situ RNA hybridization assays, we characterized the transcriptomic signatures covering nearly all cochlear cell types and developed cell type-specific markers. Three cell types were discovered; two of them contribute to the modiolus which houses the primary auditory neurons and blood vessels, and the third one consists in cells lining the scala vestibuli. The results also shed light on the molecular basis of the tonotopic gradient of the biophysical characteristics of the basilar membrane that critically underlies cochlear passive sound frequency analysis. Finally, overlooked expression of deafness genes in several cochlear cell types was also unveiled. This atlas paves the way for the deciphering of the gene regulatory networks controlling cochlear cell differentiation and maturation, essential for the development of effective targeted treatments.
Topics: Animals; Mice; Transcriptome; Cochlea; Basilar Membrane; Hearing; Deafness
PubMed: 37339214
DOI: 10.1073/pnas.2221744120 -
Cold Spring Harbor Perspectives in... Jun 2019This review summarizes paleontological data as well as studies on the morphology, function, and molecular evolution of the cochlea of living mammals (monotremes,... (Review)
Review
This review summarizes paleontological data as well as studies on the morphology, function, and molecular evolution of the cochlea of living mammals (monotremes, marsupials, and placentals). The most parsimonious scenario is an early evolution of the characteristic organ of Corti, with inner and outer hair cells and nascent electromotility. Most remaining unique features, such as loss of the lagenar macula, coiling of the cochlea, and bony laminae supporting the basilar membrane, arose later, after the separation of the monotreme lineage, but before marsupial and placental mammals diverged. The question of when hearing sensitivity first extended into the ultrasonic range (defined here as >20 kHz) remains speculative, not least because of the late appearance of the definitive mammalian middle ear. The last significant change was optimizing the operating voltage range of prestin, and thus the efficiency of the outer hair cells' amplifying action, in the placental lineage only.
Topics: Animals; Biological Evolution; Cochlea; Hair Cells, Auditory, Outer; Humans; Mammals; Microscopy, Electron, Scanning; Monotremata
PubMed: 30181353
DOI: 10.1101/cshperspect.a033241 -
Brain Sciences Mar 2022To date, objective measurements and psychophysical experiments have been used to measure frequency dependent basilar membrane (BM) delays in humans; however, in vivo...
To date, objective measurements and psychophysical experiments have been used to measure frequency dependent basilar membrane (BM) delays in humans; however, in vivo measurements have not been made. This study aimed to measure BM delays by performing intracochlear electrocochleography in cochlear implant recipients. Sixteen subjects with various degrees of hearing abilities were selected. Postoperative Computer Tomography was performed to determine electrode locations. Electrical potentials in response to acoustic tone pips at 0.25, 0.5, 1, 2, and 4 kHz and clicks were recorded with electrodes at the frequency specific region. The electrode array was inserted up to the characteristic cochlear frequency region of 250 Hz for 6 subjects. Furthermore, the array was inserted in the region of 500 Hz for 15 subjects, and 1, 2, and 4 kHz were reached in all subjects. Intracochlear electrocochleography for each frequency-specific tone pip and clicks showed detectable responses in all subjects. The latencies differed among the cochlear location and the cochlear microphonic (CM) onset latency increased with decreasing frequency and were consistent with click derived band technique. Accordingly, BM delays in humans could be derived. The BM delays increased systematically along the cochlea from basal to apical end and were in accordance with Ruggero and Temchin, 2007.
PubMed: 35326357
DOI: 10.3390/brainsci12030400 -
Scientific Reports Nov 2022The prevailing theory of cochlear function states that outer hair cells amplify sound-induced vibration to improve hearing sensitivity and frequency specificity. Recent...
The prevailing theory of cochlear function states that outer hair cells amplify sound-induced vibration to improve hearing sensitivity and frequency specificity. Recent micromechanical measurements in the basal turn of gerbil cochleae through the round window have demonstrated that the reticular lamina vibration lags the basilar membrane vibration, and it is physiologically vulnerable not only at the best frequency but also at the low frequencies. These results suggest that outer hair cells from a broad cochlear region enhance hearing sensitivity through a global hydromechanical mechanism. However, the time difference between the reticular lamina and basilar membrane vibration has been thought to result from a systematic measurement error caused by the optical axis non-perpendicular to the cochlear partition. To address this concern, we measured the reticular lamina and basilar membrane vibrations in the transverse direction through an opening in the cochlear lateral wall in this study. Present results show that the phase difference between the reticular lamina and basilar membrane vibration decreases with frequency by ~ 180 degrees from low frequencies to the best frequency, consistent with those measured through the round window. Together with the round-window measurement, the low-coherence interferometry through the cochlear lateral wall demonstrates that the time difference between the reticular lamina and basilar membrane vibration results from the cochlear active processing rather than a measurement error.
Topics: Animals; Basilar Membrane; Gerbillinae; Vibration; Cochlea; Hair Cells, Auditory, Outer
PubMed: 36396720
DOI: 10.1038/s41598-022-24394-0 -
The Journal of Neuroscience : the... Nov 2022The outer hair cells in the mammalian cochlea are cellular actuators essential for sensitive hearing. The geometry and stiffness of the structural scaffold surrounding...
The outer hair cells in the mammalian cochlea are cellular actuators essential for sensitive hearing. The geometry and stiffness of the structural scaffold surrounding the outer hair cells will determine how the active cells shape mammalian hearing by modulating the organ of Corti (OoC) vibrations. Specifically, the tectorial membrane and the Deiters cell are mechanically in series with the hair bundle and soma, respectively, of the outer hair cell. Their mechanical properties and anatomic arrangement must determine the relative motion among different OoC structures. We measured the OoC mechanics in the cochleas acutely excised from young gerbils of both sexes at a resolution fine enough to distinguish the displacement of individual cells. A three-dimensional finite element model of fully deformable OoC was exploited to analyze the measured data in detail. As a means to verify the computer model, the basilar membrane deformations because of static and dynamic stimulations were measured and simulated. Two stiffness ratios have been identified that are critical to understand cochlear physics, which are the stiffness of the tectorial membrane with respect to the hair bundle and the stiffness of the Deiters cell with respect to the outer hair cell body. Our measurements suggest that the Deiters cells act like a mechanical equalizer so that the outer hair cells are constrained neither too rigidly nor too weakly. Mammals can detect faint sounds thanks to the action of mammalian-specific receptor cells called the outer hair cells. It is getting clearer that understanding the interactions between the outer hair cells and their surrounding structures such as the tectorial membrane and the Deiters cell is critical to resolve standing debates. Depending on theories, the stiffness of those two structures ranges from negligible to rigid. Because of their perceived importance, their properties have been measured in previous studies. However, nearly all existing data were obtained (after they were detached from the outer hair cells), which obscures their interaction with the outer hair cells. We quantified the mechanical properties of the tectorial membrane and the Deiters cell .
Topics: Male; Animals; Female; Hair Cells, Auditory, Outer; Organ of Corti; Basilar Membrane; Tectorial Membrane; Cochlea; Hair Cells, Vestibular; Gerbillinae
PubMed: 36123119
DOI: 10.1523/JNEUROSCI.2417-21.2022