-
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 -
Hearing Research Mar 2018The motion along the basilar membrane in the cochlea is due to the interaction between the micromechanical behaviour of the organ of Corti and the fluid movement in the... (Review)
Review
The motion along the basilar membrane in the cochlea is due to the interaction between the micromechanical behaviour of the organ of Corti and the fluid movement in the scalae. By dividing the length of the cochlea into a finite number of elements and assuming a given radial distribution of the basilar membrane motion for each element, a set of equations can be separately derived for the micromechanics and for the fluid coupling. These equations can then be combined, using matrix methods, to give the fully coupled response. This elemental approach reduces to the classical transmission line model if the micromechanics are assumed to be locally-reacting and the fluid coupling is assumed to be entirely one-dimensional, but is also valid without these assumptions. The elemental model is most easily formulated in the frequency domain, assuming quasi-linear behaviour, but a time domain formulation, using state space method, can readily incorporate local nonlinearities in the micromechanics. Examples of programs are included for the elemental model of a human cochlea that can be readily modified for other species.
Topics: Acoustic Stimulation; Auditory Pathways; Cochlea; Computer Simulation; Finite Element Analysis; Hearing; Humans; Hydrodynamics; Models, Theoretical; Motion; Sound; Time Factors
PubMed: 29174619
DOI: 10.1016/j.heares.2017.10.013 -
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 -
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 -
Proceedings of the National Academy of... Aug 2016It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar...
It is commonly believed that the exceptional sensitivity of mammalian hearing depends on outer hair cells which generate forces for amplifying sound-induced basilar membrane vibrations, yet how cellular forces amplify vibrations is poorly understood. In this study, by measuring subnanometer vibrations directly from the reticular lamina at the apical ends of outer hair cells and from the basilar membrane using a custom-built heterodyne low-coherence interferometer, we demonstrate in living mouse cochleae that the sound-induced reticular lamina vibration is substantially larger than the basilar membrane vibration not only at the best frequency but surprisingly also at low frequencies. The phase relation of reticular lamina to basilar membrane vibration changes with frequency by up to 180 degrees from ∼135 degrees at low frequencies to ∼-45 degrees at the best frequency. The magnitude and phase differences between reticular lamina and basilar membrane vibrations are absent in postmortem cochleae. These results indicate that outer hair cells do not amplify the basilar membrane vibration directly through a local feedback as commonly expected; instead, they actively vibrate the reticular lamina over a broad frequency range. The outer hair cell-driven reticular lamina vibration collaboratively interacts with the basilar membrane traveling wave primarily through the cochlear fluid, which boosts peak responses at the best-frequency location and consequently enhances hearing sensitivity and frequency selectivity.
Topics: Acoustic Stimulation; Animals; Basement Membrane; Basilar Membrane; Cochlea; Female; Hair Cells, Auditory, Outer; Hearing; Interferometry; Male; Mechanotransduction, Cellular; Mice, Inbred CBA; Sound; Vibration
PubMed: 27516544
DOI: 10.1073/pnas.1607428113 -
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 -
Frontiers in Cellular Neuroscience 2023Age-related hearing loss (ARHL) is the most common sensory degenerative disease and can significantly impact the quality of life in elderly people. A previous study...
Age-related hearing loss (ARHL) is the most common sensory degenerative disease and can significantly impact the quality of life in elderly people. A previous study using GeneChip miRNA microarray assays showed that the expression of miR-29a changes with age, however, its role in hearing loss is still unclear. In this study, we characterized the cochlear phenotype of miR-29a knockout () mice and found that miR-29a-deficient mice had a rapid progressive elevation of the hearing threshold from 2 to 5 months of age compared with littermate controls as measured by the auditory brainstem response. Stereocilia degeneration, hair cell loss and abnormal stria vascularis (SV) were observed in mice at 4 months of age. Transcriptome sequencing results showed elevated extracellular matrix (ECM) gene expression in mice. Both Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the key differences were closely related to ECM. Further examination with a transmission electron microscope showed thickening of the basilar membrane in the cochlea of mice. Five Col4a genes () and two laminin genes () were validated as miR-29a direct targets by dual luciferase assays and miR-29a inhibition assays with a miR-29a inhibitor. Consistent with the target gene validation results, the expression of these genes was significantly increased in the cochlea of mice, as shown by RT-PCR and Western blot. These findings suggest that miR-29a plays an important role in maintaining cochlear structure and function by regulating the expression of collagen and laminin and that the disturbance of its expression could be a cause of progressive hearing loss.
PubMed: 37275774
DOI: 10.3389/fncel.2023.1191740 -
BioMed Research International 2014The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic... (Review)
Review
The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane (BM). Sounds enter the fluid-filled cochlea and cause deflection of the BM due to pressure differences between the cochlear fluid chambers. These deflections travel along the cochlea, increasing in amplitude, until a frequency-dependent characteristic position and then decay away rapidly. The hair cells can detect these deflections and encode them as neural signals. Modelling the mechanics of the cochlea is of help in interpreting experimental observations and also can provide predictions of the results of experiments that cannot currently be performed due to technical limitations. This paper focuses on reviewing the numerical modelling of the mechanical and electrical processes in the cochlea, which include fluid coupling, micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling.
Topics: Basilar Membrane; Biomechanical Phenomena; Hair Cells, Auditory; Hearing; Humans; Models, Biological
PubMed: 25136555
DOI: 10.1155/2014/150637