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Development (Cambridge, England) Jun 2020The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the... (Review)
Review
The cochlea, a coiled structure located in the ventral region of the inner ear, acts as the primary structure for the perception of sound. Along the length of the cochlear spiral is the organ of Corti, a highly derived and rigorously patterned sensory epithelium that acts to convert auditory stimuli into neural impulses. The development of the organ of Corti requires a series of inductive events that specify unique cellular characteristics and axial identities along its three major axes. Here, we review recent studies of the cellular and molecular processes regulating several aspects of cochlear development, such as axial patterning, cochlear outgrowth and cellular differentiation. We highlight how the precise coordination of multiple signaling pathways is required for the successful formation of a complete organ of Corti.
Topics: Animals; Auditory Perception; Cell Differentiation; Cochlea; Hair Cells, Auditory; Mitosis; Organ of Corti; SOXB1 Transcription Factors; Signal Transduction
PubMed: 32571852
DOI: 10.1242/dev.162263 -
Cold Spring Harbor Perspectives in... Sep 2019Over 450 million people worldwide suffer from hearing loss, leading to an estimated economic burden of ∼$750 billion. The past decade has seen significant advances in... (Review)
Review
Over 450 million people worldwide suffer from hearing loss, leading to an estimated economic burden of ∼$750 billion. The past decade has seen significant advances in the understanding of the molecular mechanisms that contribute to hearing, and the environmental and genetic factors that can go awry and lead to hearing loss. This in turn has sparked enormous interest in developing gene therapy approaches to treat this disorder. This review documents the most recent advances in cochlear gene therapy to restore hearing loss, and will cover viral vectors and construct designs, potential routes of delivery into the inner ear, and, lastly, the most promising genes of interest.
Topics: Animals; Cochlea; Genetic Therapy; Genetic Vectors; Hearing Loss; Humans
PubMed: 30323014
DOI: 10.1101/cshperspect.a033191 -
Audiology & Neuro-otology 2022The auditory system processes how we hear and understand sounds within the environment. It comprises both peripheral and central structures. Sympathetic nervous system... (Review)
Review
BACKGROUND
The auditory system processes how we hear and understand sounds within the environment. It comprises both peripheral and central structures. Sympathetic nervous system projections are present throughout the auditory system. The function of sympathetic fibers in the cochlea has not been studied extensively due to the limited number of direct projections in the auditory system. Nevertheless, research on adrenergic and noradrenergic regulation of the cochlea and central auditory system is growing. With the rapid development of neuroscience, auditory central regulation is an extant topic of focus in research on hearing.
SUMMARY
As such, understanding sympathetic nervous system regulation of auditory function is a growing topic of interest. Herein, we review the distribution and putative physiological and pathological roles of sympathetic nervous system projections in hearing.
KEY MESSAGES
In the peripheral auditory system, the sympathetic nervous system regulates cochlear blood flow, modulates cochlear efferent fibers, affects hair cells, and influences the habenula region. In central auditory pathways, norepinephrine is essential for plasticity in the auditory cortex and affects auditory cortex activity. In pathological states, the sympathetic nervous system is associated with many hearing disorders. The mechanisms and pathways of sympathetic nervous system modulation of auditory function is still valuable for us to research and discuss.
Topics: Auditory Pathways; Cochlea; Hair Cells, Auditory; Hearing; Sympathetic Nervous System
PubMed: 34407531
DOI: 10.1159/000517452 -
Cold Spring Harbor Perspectives in... Apr 2019In sharp contrast to the adult mammalian cochlea, which lacks regenerative ability, the mature avian cochlea, or basilar papilla (BP) is capable of complete recovery... (Review)
Review
In sharp contrast to the adult mammalian cochlea, which lacks regenerative ability, the mature avian cochlea, or basilar papilla (BP) is capable of complete recovery from hearing loss after damage. Avian sensory hair cell regeneration relies on rousing quiescent supporting cells to proliferate or transdifferentiate after hair cell death. Unlike mammalian cochlear supporting cells, which have clearly defined subtypes, avian BP supporting cells are deceptively indistinguishable and molecular markers have yet to be identified. Despite the importance of supporting cells as the putative stem cells in avian regeneration, it is unknown whether all supporting cells possess equal capability to give rise to a hair cell or if a specialized subpopulation exists. In this perspective, we reinvigorate the concept of a stem cell in the BP, and form comparisons to other regenerating tissues that show cell-cycle reentry after damage. Special emphasis is given to the structure of the BP and how anatomy informs both the potential, intrinsic heterogeneity of the supporting cell layer as well as the choice between mitotic and nonmitotic regenerative strategies.
Topics: Animals; Birds; Cell Cycle; Cochlea; Hair Cells, Auditory; Regeneration; Stem Cells
PubMed: 30249599
DOI: 10.1101/cshperspect.a033183 -
Journal of the Association For Research... Dec 2012Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in... (Review)
Review
Evolution of the cochlea and high-frequency hearing (>20 kHz; ultrasonic to humans) in mammals has been a subject of research for many years. Recent advances in paleontological techniques, especially the use of micro-CT scans, now provide important new insights that are here reviewed. True mammals arose more than 200 million years (Ma) ago. Of these, three lineages survived into recent geological times. These animals uniquely developed three middle ear ossicles, but these ossicles were not initially freely suspended as in modern mammals. The earliest mammalian cochleae were only about 2 mm long and contained a lagena macula. In the multituberculate and monotreme mammalian lineages, the cochlea remained relatively short and did not coil, even in modern representatives. In the lineage leading to modern therians (placental and marsupial mammals), cochlear coiling did develop, but only after a period of at least 60 Ma. Even Late Jurassic mammals show only a 270 ° cochlear coil and a cochlear canal length of merely 3 mm. Comparisons of modern organisms, mammalian ancestors, and the state of the middle ear strongly suggest that high-frequency hearing (>20 kHz) was not realized until the early Cretaceous (~125 Ma). At that time, therian mammals arose and possessed a fully coiled cochlea. The evolution of modern features of the middle ear and cochlea in the many later lineages of therians was, however, a mosaic and different features arose at different times. In parallel with cochlear structural evolution, prestins in therian mammals evolved into effective components of a new motor system. Ultrasonic hearing developed quite late-the earliest bat cochleae (~60 Ma) did not show features characteristic of those of modern bats that are sensitive to high ultrasonic frequencies.
Topics: Animals; Anion Transport Proteins; Biological Evolution; Cochlea; Hearing; Humans; Mammals; Sulfate Transporters
PubMed: 22983571
DOI: 10.1007/s10162-012-0349-9 -
Pharmacology & Therapeutics Aug 2019An estimated 466 million people suffer from hearing loss worldwide. Sensorineural hearing loss is characterized by degeneration of key structures of the sensory pathway... (Review)
Review
An estimated 466 million people suffer from hearing loss worldwide. Sensorineural hearing loss is characterized by degeneration of key structures of the sensory pathway in the cochlea such as the sensory hair cells, the primary auditory neurons and their synaptic connection to the hair cells - the ribbon synapse. Various strategies to protect or regenerate these sensory cells and structures are the subject of intensive research. Yet despite recent advances in our understandings of the capacity of the cochlea for repair and regeneration there are currently no pharmacological or biological interventions for hearing loss. Current research focusses on localized cochlear drug, gene and cell-based therapies. One of the more promising drug-based therapies is based on neurotrophic factors for the repair of the ribbon synapse after noise exposure, as well as preventing loss of primary auditory neurons and regrowth of the auditory neuron fibers after severe hearing loss. Drug therapy delivery technologies are being employed to address the specific needs of neurotrophin and other therapies for hearing loss that include the need for high doses, long-term delivery, localised or cell-specific targeting and techniques for their safe and efficacious delivery to the cochlea. Novel biomaterials are enabling high payloads of drugs to be administered to the cochlea with subsequent slow-release properties that are proving to be beneficial for treating hearing loss. In parallel, new gene therapy technologies are addressing the need for cell specificity and high efficacy for the treatment of both genetic and acquired hearing loss with promising reports of hearing recovery. Some biomaterials and cell therapies are being used in conjunction with the cochlear implant ensuring therapeutic benefit to the primary neurons during electrical stimulation. This review will introduce the auditory system, hearing loss and the potential for repair and regeneration in the cochlea. Drug delivery to the cochlea will then be reviewed, with a focus on new biomaterials, gene therapy technologies, cell therapy and the use of the cochlear implant as a vehicle for drug delivery. With the current pre-clinical research effort into therapies for hearing loss, including clinical trials for gene therapy, the future for the treatment for hearing loss is looking bright.
Topics: Animals; Biocompatible Materials; Cell- and Tissue-Based Therapy; Cochlea; Cochlear Implants; Drug Delivery Systems; Genetic Therapy; Hearing Loss; Humans
PubMed: 31075354
DOI: 10.1016/j.pharmthera.2019.05.003 -
Physiological Reviews Jul 2001In mammals, environmental sounds stimulate the auditory receptor, the cochlea, via vibrations of the stapes, the innermost of the middle ear ossicles. These vibrations... (Review)
Review
In mammals, environmental sounds stimulate the auditory receptor, the cochlea, via vibrations of the stapes, the innermost of the middle ear ossicles. These vibrations produce displacement waves that travel on the elongated and spirally wound basilar membrane (BM). As they travel, waves grow in amplitude, reaching a maximum and then dying out. The location of maximum BM motion is a function of stimulus frequency, with high-frequency waves being localized to the "base" of the cochlea (near the stapes) and low-frequency waves approaching the "apex" of the cochlea. Thus each cochlear site has a characteristic frequency (CF), to which it responds maximally. BM vibrations produce motion of hair cell stereocilia, which gates stereociliar transduction channels leading to the generation of hair cell receptor potentials and the excitation of afferent auditory nerve fibers. At the base of the cochlea, BM motion exhibits a CF-specific and level-dependent compressive nonlinearity such that responses to low-level, near-CF stimuli are sensitive and sharply frequency-tuned and responses to intense stimuli are insensitive and poorly tuned. The high sensitivity and sharp-frequency tuning, as well as compression and other nonlinearities (two-tone suppression and intermodulation distortion), are highly labile, indicating the presence in normal cochleae of a positive feedback from the organ of Corti, the "cochlear amplifier." This mechanism involves forces generated by the outer hair cells and controlled, directly or indirectly, by their transduction currents. At the apex of the cochlea, nonlinearities appear to be less prominent than at the base, perhaps implying that the cochlear amplifier plays a lesser role in determining apical mechanical responses to sound. Whether at the base or the apex, the properties of BM vibration adequately account for most frequency-specific properties of the responses to sound of auditory nerve fibers.
Topics: Animals; Cochlea; Mammals; Vibration
PubMed: 11427697
DOI: 10.1152/physrev.2001.81.3.1305 -
BMB Reports Oct 2017Mammalian inner ear comprises of six sensory organs; cochlea, utricle, saccule, and three semicircular canals. The cochlea contains sensory epithelium known as the organ... (Review)
Review
Mammalian inner ear comprises of six sensory organs; cochlea, utricle, saccule, and three semicircular canals. The cochlea contains sensory epithelium known as the organ of Corti which senses sound through mechanosensory hair cells. Mammalian inner ear undergoes series of morphogenesis during development beginning thickening of ectoderm nearby hindbrain. These events require tight regulation of multiple signaling cascades including FGF, Wnt, Notch and Bmp signaling. In this review, we will discuss the role of newly emerging signaling, FGF signaling, for its roles required for cochlear development. [BMB Reports 2017; 50(10): 487-495].
Topics: Animals; Cell Differentiation; Cochlea; Fibroblast Growth Factors; Humans; Morphogenesis; Signal Transduction
PubMed: 28855028
DOI: 10.5483/bmbrep.2017.50.10.164 -
Journal of Anatomy Feb 2016The mammalian cochlea is a remarkable sensory organ, capable of perceiving sound over a range of 10(12) in pressure, and discriminating both infrasonic and ultrasonic... (Review)
Review
The mammalian cochlea is a remarkable sensory organ, capable of perceiving sound over a range of 10(12) in pressure, and discriminating both infrasonic and ultrasonic frequencies in different species. The sensory hair cells of the mammalian cochlea are exquisitely sensitive, responding to atomic-level deflections at speeds on the order of tens of microseconds. The number and placement of hair cells are precisely determined during inner ear development, and a large number of developmental processes sculpt the shape, size and morphology of these cells along the length of the cochlear duct to make them optimally responsive to different sound frequencies. In this review, we briefly discuss the evolutionary origins of the mammalian cochlea, and then describe the successive developmental processes that lead to its induction, cell cycle exit, cellular patterning and the establishment of topologically distinct frequency responses along its length.
Topics: Animals; Biological Evolution; Cochlea; Hearing; Mammals
PubMed: 26052920
DOI: 10.1111/joa.12314 -
Hearing Research May 2018The cochlea has an immune environment dominated by macrophages under resting conditions. When stressed, circulating monocytes enter the cochlea. These immune mediators,... (Review)
Review
The cochlea has an immune environment dominated by macrophages under resting conditions. When stressed, circulating monocytes enter the cochlea. These immune mediators, along with cochlear resident cells, organize a complex defense response against pathological challenges. Since the cochlea has minimal exposure to pathogens, most inflammatory conditions in the cochlea are sterile. Although the immune response is initiated for the protection of the cochlea, off-target effects can cause collateral damage to cochlear cells. A better understanding of cochlear immune capacity and regulation would therefore lead to development of new therapeutic treatments. Over the past decade, there have been many advances in our understanding of cochlear immune capacity. In this review, we provide an update and overview of the cellular components of cochlear immune capacity with a focus on macrophages in mammalian cochleae. We describe the composition and distribution of immune cells in the cochlea and suggest that phenotypic and functional characteristics of macrophages have site-specific diversity. We also highlight the response of immune cells to acute and chronic stresses and comment on the potential function of immune cells in cochlear homeostasis and disease development. Finally, we briefly review potential roles for cochlear resident cells in immune activities of the cochlea.
Topics: Animals; Cellular Microenvironment; Chemotaxis, Leukocyte; Cochlea; Homeostasis; Humans; Leukocytes; Macrophage Activation; Macrophages; Phenotype; Signal Transduction; Stress, Physiological
PubMed: 29310977
DOI: 10.1016/j.heares.2017.12.009