Do Sensory Hair Cells Register Impact

Diseases of the ear

Anastasia P. Nesterova , ... Anton Yuryev , in Disease Pathways, 2020

Primal cellular contributors and processes

Cochlear hair jail cell

Prison cell

Cochlear hair cells are the sensory cells of the auditory organization. These cells possess stereocilia continued to the tectorial membrane. During auditory stimulation, audio waves in the cochlea cause deflection of the hair cell stereocilia, which creates an electrical betoken in the hair cell.

Cochlear

Anatomic structure

Cochlea is a snail-shaped canal in the osseous labyrinth of the inner ear, which contains the sensory organ of hearing—the organ of Corti.

Inner ear

Anatomic structure

The inner ear is the innermost portion of the ear that contains organs responsible for hearing and the sense of balance. Located in the temporal bone, the inner ear has 3 essential parts: cochlea, lobby, and semicircular canals.

Mechanoelectrical transducer channel

Anatomic construction

The mechanoelectrical transducer (MET) channels are ion channels on the tips of stereocilia. Deflection of stereocilia provokes mechanical opening of these channels and the entrance of cations that generates action potential.

Organ of Corti

Anatomic structure

The organ of Corti is the auditory organ situated in the cochlea of the inner ear. The sensory hair cells that make up the organ of Corti are responsible for the transduction of the auditory impulse into neural signals.

Ribbon synapses

Cell

A ribbon synapse is a neuronal synapse structurally unlike from other synapses by the presence of an electron-dense structure called synaptic ribbon, which helps to keep synaptic vesicles near the agile zone. Ribbon synapses are establish in various sensory receptor cells, for example, auditory hair cells of the cochlea, and characterized past increased performance.

Stereocilia

Anatomic structure

Stereocilia are thin projections on the cochlear hair cells that respond to fluid motion and are involved in mechanosensing. Despite a similar proper name, stereocilia are dissimilar from cilia (microtubule cytoskeleton–based structures) and comprise actin cytoskeleton, similarly to microvilli.

Tectorial membrane

Anatomic structure

The tectorial membrane is a band of extracellular matrix in the cochlea located above the inner and outer hair cells of the organ of Corti. The tectorial membrane is connected to stereocilia of the outer pilus cells and participates in mechanotransduction. During auditory stimulation the tectorial membrane directly stimulates the outer pilus cells and creates liquid movements that stimulate the inner hair cells.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128170861000075

Epidemiology, Etiology and Genetics of Hearing Issues

Jos J. Eggermont , in Noise and the Brain, 2014

2.2.one What Goes Wrong in NIHL?

Cochlear pilus jail cell damage by reactive oxygen species (ROS) post-obit noise exposure is a potential mechanism for NIHL. Superoxide anion radicals are plant in the stria vascularis after intense dissonance exposure ⁵⁶ and hydroxyl radicals significantly increase in the cochlea of animals exposed to noise. ⁵⁷ It is known that antioxidant therapy protects against NIHL (Chapter 12), whereas chemicals that produce oxidative stress potentiate NIHL. ⁵⁸ Several ROS are generated in the cochlea under normal metabolic circumstances during the reduction of oxygen into Oⁱⁱ⁻ (i.e., O₂ into H₂O). Antioxidant systems neutralize these ROS. Likewise antioxidant enzymes another set up of enzymes (eastward.m., catalase) is involved in the breakup of superoxide anions and hydrogen peroxide (H₂O₂). In the inner ear, college levels of catalase are observed in the organ of Corti than in the stria vascularis. ⁵⁹ The large individual variability in susceptibility to noise, in humans as well as animals, indicates that genetic factors play a role in the development of NIHL.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780124159945000026

Management of Developed Sensorineural Hearing Loss

Dr. Justin T. Lui Dr. , ... Dr. Justin K. Chau Md , in Testify-Based Clinical Practice in Otolaryngology, 2018

Noise-Induced Hearing Loss

Cochlear hair cell injury occurs through mechanical trauma and metabolic injury in response to high-intensity noise exposure. Mechanical destruction of hair cells and supporting structures has been identifiable in the medical literature for several decades. ³⁵ More recently, animal studies have identified iii metabolic pathways that contribute to noise-induced hearing loss (NIHL), including calcium overload, reactive oxidative species, and mitochondrial pathways. ³⁵

Excessive recreational and/or occupational racket is recognized as a key correspondent to permanent hearing loss with nigh 500 million individuals at risk of developing NIHL. ^36,37 Hazardous occupational racket exposure affects an estimated 22 1000000 US workers. ^36,37 Despite being the mainstay of hearing loss prevention, hearing protection devices compliance is estimated to be only 34.3% in individuals exposed to hazardous noise volumes. ³⁶ Moreover, an estimated 1.1 billion young adults are at risk of hearing loss secondary to dissonance exposure from nightclubs, sporting events, and personal audio devices. ³⁸ When comparing the prevalence of the incidence of hearing loss from ages 12 to 19 years, the National Wellness and Nutrition Test Survey identified an increase in hearing loss prevalence from 3.5% to 5.iii% from 1994 to 2006, respectively. ³⁹

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780323544603000026

Repairing and Building New Ears

Jos J. Eggermont , in Hearing Loss, 2017

13.2 Regenerating Hair Cells

Cochlear hair cells are susceptible to damage from a variety of sources (see chapters: Causes of Caused Hearing Loss; Epidemiology and Genetics of Hearing Loss and Tinnitus chapter: Causes of Caused Hearing Loss affiliate: Epidemiology and Genetics of Hearing Loss and Tinnitus ). The consequence of this damage in humans frequently is permanent hearing loss. The discovery that hair cells can regenerate in birds and other non-mammalian vertebrates has led to various attempts of restoring hearing subsequently such damage. After reviewing the early on findings that atomic number 82 to these studies, we will describe the various ways in which inner ear office in humans may eventually be restored.

According to Fukui and Raphael (2013), in one case the ear shows pilus prison cell loss, protection is no longer an option and efforts need to be dedicated to hair cell regeneration. This may be achieved by manipulating prison cell proliferation control (Chen and Segil, 1999; Lowenheim et al., 1999) or by influencing expression of genes that specify pilus cell differentiation. The latter studies mostly involved regulating expression of Atoh1 for which it was shown that the duration of expression is critical for hair cell survival and for the type of hair jail cell that is generated (Pan et al., 2012). The hair cells that are generated by induced Atoh1 expression result from transdifferentiation of nonsensory cells in the organ of Corti. Information technology has been demonstrated that the possibility for this transdifferentiation is gradually reduced every bit the cochlea matures (Kelly et al., 2012; Liu et al., 2012).

Read full affiliate

URL:

https://www.sciencedirect.com/science/article/pii/B978012805398000013X

Gangliosides in Health and Disease

Jin-ichi Inokuchi , ... Fumi Shishido , in Progress in Molecular Biological science and Translational Science, 2018

half-dozen.4 GM3-Enriched Membrane Organization, PTPRQ-Myosin VI Complex Localization and Hair Cell Morphology

Cochlear hair cells are specialized for auditory and vestibular transduction. Projecting from their apical surface are filopodial processes (stereocilia) that contain hundreds of cross-linked actin filaments. Proteins, such every bit anarchistic myosins, Conductor proteins, and deafness-related gene products [protein Tyr phosphatase receptor Q (PTPRQ), cadherin23, protocadherin15, usherin, VLGR1] are expressed predominantly or exclusively in stereocilia, forming a structured interactive network for mechanoelectrical transduction. ¹⁸⁶

In the normal organ of Corti, functional PTPRQ-myosin Half dozen complexes are essential to maintain integrity of this network. ¹⁸⁷ PTPRQ, a shaft connector at the tapered base of stereocilia, consists of an extracellular domain with 18 fibronectin III (FNIII) repeats, a membrane spanning domain, and a cytoplasmic domain having phosphatidylinositol and Tyr phosphatase activities. ^187,188 Myosin VI is an actin-based motor poly peptide whose complex with PTPRQ mediates interactions between plasma membrane and cytoskeleton. ¹⁸⁹ PTPRQ-deficient mice are deaf and accept fused stereocilia that exercise not taper at the base. ¹⁹⁰ Myosin Half-dozen-scarce mice are as well deafened and take comparable structural changes of pilus cells, accompanied by maldistribution of PTPRQ along the stereocilia. ^190–192

In bullfrogs (Rana catesbeiana), PTPRQ is colocalized with ganglioside-rich membrane domains in basal stereocilia. ¹⁹³ We examined the relationship betwixt gangliosides and basal PTPRQ-myosin Half-dozen complex by immunostaining (Fig. 7). PTPRQ is localized exclusively in bases of stereocilia in WT murine IHCs. In dissimilarity, in GM3S-null mice PTPRQ is maldistributed along shafts of fused stereocilia (Fig. 7B), and myosin VI is nowadays from base of operations to midshaft but absent-minded from distal regions (Fig. viiA). These structural disruptions presumably result in loss of normal ciliary motor action. In OHCs of GM3S-null mice, myosin VI is expressed mostly at the cuticular plate surface, close to vestigial kinocilia.

These findings, taken together, indicate that GM3-enriched membrane microdomains are essential for formation and proper localization of PTPRQ-myosin Half dozen complexes in hair cells. Aberrant expression of PTPRQ-myosin Vi complexes resulting from absence of GM3 alters the structure of stereocilia and impairs their ability to transduce auditory signals (Fig. 7C).

Read full affiliate

URL:

https://www.sciencedirect.com/science/article/pii/S1877117317301412

Functional Circuit Development in the Auditory Arrangement

D.B. Polley , ... J.T. Sanchez , in Neural Circuit Development and Function in the Brain, 2013

2.ii.1 Developing Networks Within the Cochlea

Cochlear hair cells initiate the process of hearing by converting mechanical deflections of their stereocilia bundles into electrochemical signals that are distributed throughout the balance of the auditory system. Earlier mature and normal transduction can occur, a number of critical developmental events take place between pilus cells and non-sensory cells inside the cochlea. The specialized office of IHCs and OHCs depends in function upon developing networks of non-sensory supporting cells within the organ of Corti and the lateral wall of the cochlea.

The precision of mechanoelectrical transduction tin can be attributed, in function, to the unusual electrical potential and ionic milieu in the endolymphatic space surrounding the upmost surface of the pilus cell. Prior to and during the first week of hearing, an endocochlear potential is established between the endolymph and surrounding perilymph, which increases from 0 mV to + 80 mV. The ramping upwardly of the electric potential is complemented by the accumulation of high levels of Thousand⁺ in the endolymphatic infinite, which further exaggerates the electrical gradient beyond the negative resting potential of the hair cell membrane. The combination of high extracellular M⁺ and the positive endocochlear potential work synergistically to effectively drive ionic currents through open mechanotransducer channels, creating the large and rapid receptor potential changes that mediate glutamate release at the synapse betwixt the hair prison cell and the auditory nerve. The endocochlear potential is established through the evolution of tight cellular junctions between local networks of epithelial cells, connective tissue and supporting cells that completely partition the endolymph from the surrounding perilymph. These tightly bound networks also efficiently recycle K⁺ from the hair cell back into the endolymphatic infinite where they can once again be used in sensory transduction.

The spontaneous generation of activity potentials from sensory receptors is considered essential for normal neural circuit development throughout the brain. In the developing auditory system, the mechanisms responsible for spontaneous action potential activity are nevertheless unresolved but contempo reports propose that this spontaneous activity is generated by IHCs of the cochlea. The cartoon of the IHC region in the immature Organ of Corti represents one proposed set of developmental changes that occur in cochlear circuitry (Effigy two.1(a)). Compared to IHCs in mature animals, which are surrounded by one or ii supporting cells (run across Figure 2.ane(a)), the pre-hearing Organ of Corti features a structure known as the greater epithelial ridge, or Kollikers organ (Ko). This construction consists of not-neuronal inner supporting cells (ISCs) that are nowadays up to the onset of hearing. Nonetheless, by the fourth dimension of hearing onset, Ko undergoes programmed cell expiry and subsequent removal of the majority of ISCs. Despite this dramatic change in the structure of the organ of Corti, recent studies accept identified a potential role for ISCs in the initiation of electrical signaling within the auditory nerve (Tritsch, 2007). Ane to ii weeks prior to the onset of hearing, the elongated ISCs within Ko brainstorm to spontaneously release adenosine tri-phosphate (ATP) into the extracellular space (Figure 2.2(b)). ATP activates purinergic receptors on neighboring IHCs, peripheral processes of the auditory nerve and on the ISCs themselves. Bounden of ATP on the IHC depolarizes the membrane potential, inducing Ca^{2 +}-dependent glutamate release and bursts of action potentials in auditory nervus fibers. ATP release is local and desynchronized along the length of the cochlea. In this manner, spatially and temporally independent volleys of electric signals initiated past not-sensory neurons entrain the firing patterns of SG and, ultimately, central auditory neurons. This process is thought to play a role in the strengthening of functional circuits prior to the onset of hearing.

Despite this role of ATP release from Ko, it remains uncertain how early activeness potential activity is patterned and whether ATP binding drives IHC membrane voltage or provides weaker modulatory control. More than contempo information suggests that during the first postnatal week of life, developing IHCs intrinsically generate the voltage changes that elicit activeness potentials in SG neurons. The frequency and design of this spontaneous action potential activity varies between regions of the cochlea (i.eastward., high-frequency versus low-frequency) and are modulated in multiple means past the release of acetylcholine (ACh) and ATP near the IHCs (Johnson, 2011). Information technology has been proposed that this pattern of action potential activity, along with ACh and ATP modulation, could be important for guiding tonotopic organization and the refinement of sensory information along the central auditory pathways before the occurrence of experience-bulldoze information becomes relevant.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780123972675001369

Diagnosis and Rehabilitation of Hearing Disorders in the Elderly

Chiemi Tanaka PhD , ... Henry Fifty. Lew MD, PhD , in Geriatric Rehabilitation, 2018

Regeneration of the cochlear hair prison cell and auditory nervus

The cochlear hair cells (mechanoreceptors in the auditory system) play an important role in sound perception. The homo temporal os studies in a patient with ARHL revealed missing and damaged hair cells, especially in the basal plough of the cochlea, contributing to high-frequency hearing loss. ^12,13 It is known that mammalian cells in many organs are constantly replenished or regenerated following injury, merely no mammalian hair cell replacement or cell proliferation was observed. Researchers found that hair cells in other vertebrates, such as avian, regenerate, ³³ and ongoing human hair cell regeneration inquiry is taking place in fauna studies, facing progress and challenges. ³⁴ On the contrary, the auditory nerve is known to degenerate after pilus jail cell expiry. Inquiry studies in preservation and regeneration of auditory nervus, as well as hair jail cell regeneration, are advancing forrard. Post-obit translational and large-scale clinical trials, regeneration of the cochlear pilus cell and auditory nerve may become a medical treatment pick in the hereafter. ³⁵

Read total chapter

URL:

https://www.sciencedirect.com/scientific discipline/article/pii/B978032354454200011X

SOX2 in Neurosensory Fate Determination and Differentiation in the Inner Ear

Kathryn Southward.Eastward. Cheah , Pin-Xian Xu , in Sox2, 2016

Perspective and Regenerative Medicine for the Inner Ear

The mammalian cochlear hair cells are known to lose proliferative capacities after they enter the differentiation stage. Different those in nonmammalian vertebrates such every bit birds and fish, lost hair cells cannot be replaced through proliferation and transdifferentiation of surrounding supporting cells. SOX2 ⁺OCT4⁺ stalk cells isolated from man fetal cochleae and human embryonic stem cell–derived otic progenitors can be induced to differentiate into sensory hair cells and neurons (Boddy et al., 2012; Chen et al., 2007, 2009, 2012). Despite progress in the quest for stalk cell-based therapies for the human inner ear, there are considerable challenges (Okano and Kelley, 2012). Because SOX2 is a primal gene controlling sensory jail cell development in the inner ear, better noesis of pilus jail cell specification and differentiation in relation to the expression of SOX2 with its partner proteins would be extremely important and beneficial for understanding of normal development of the cochlea and how to restore hearing in damaged cochlea. Identification of the critical role of SOX2 and its partner proteins has begun to elucidate the molecular events controlling neuronal or hair jail cell specification. Still, significant questions remain near the downstream targets of SOX2 and the full range of SOX2 partners: how it interacts with its partner proteins to exert positional cues to regulate specification, proliferation, differentiation, and maintenance, and what intrinsic and extrinsic mechanisms control the levels of these transcription factors. SOX2 expression is maintained in supporting cells in the adult inner ear, which, unlike those of nonmammalian vertebrates, remain quiescent even afterwards sensory hair cell impairment or loss. Although studies reported that SOX2 might regulate p27Kip1 expression in the supporting cells to maintain a quiescent state (Liu et al., 2012), the nature and molecular controls of supporting jail cell differentiation during development and the significance of persistent SOX2 expression in those cells are not well understood. To date, we do not fully sympathise why SOX2⁺ supporting cells do not respond to damage to induce re-expression of developmental regulatory genes important in embryonic development and growth. The greatest challenge to achieving transdifferentiation and regeneration is how to reactivate the molecular pathways that control hair jail cell specification, differentiation, maintenance, and function during development. Activation of Atoh1 can induce hair cell fate but ATOH1 solitary is apparently insufficient to promote hair cell differentiation, maintenance, and function. The machinery governing transdifferentiation in lower vertebrates is still not well understood, although studies in chicks suggest that ATOH1 is involved in hair jail cell regeneration (Cafaro et al., 2007). As described above, SOX2 alone is insufficient to activate robust Atoh1 transcription and it requires cofactors EYA1 and SIX1, both of which are not expressed in supporting cells in the ear. After Atoh1 activation, Sox2 also needs to be downregulated for hair cell differentiation to occur. Singled-out regulatory mechanisms for controlling Sox2 levels at different stages and prison cell types, the combinatorial code of target specificity defined by SOX2 and its distinct cofactors, as well equally chromatin regulators and its transcriptional activation and repression activities in the inner ear accept left much to exist revealed. Future studies with stage- and cell blazon–specific ChIP-seq and RNA-seq analysis and proteomics are essential for a molecular understanding of SOX2-regulatory networks in the different phases of sensory development in the inner ear and how these are disrupted in disease. A comprehensive understanding of growth control in the neurosensory progenitors, the rules that govern cellular behavior of SOX2⁺ supporting cells in adult ear, and the nature of molecular factors necessary for inducing competency of cells to reply to damage or an instructive indicate for inner ear sensory cell germination would be important in inner ear research with implications in illness such as sensorineural hearing loss.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128003527000153

Neurologic Signs in the Elderly

Rawan Tarawneh , James East. Galvin , in Brocklehurst's Textbook of Geriatric Medicine and Gerontology (Seventh Edition), 2010

Hearing and vestibular role

Gradual loss of cochlear hair cells, atrophy of the stria vascularis, and thickening of the basement membrane may account for the impaired hearing that is ordinarily seen with aging. This is often referred to as "presbycusis" and predominantly affects higher frequencies. ² Other changes include dumb speech discrimination, increase in pure tone threshold averages (approximately 2 dB/yr), and decreased bigotry scores. ³⁵

Vestibular role may also be afflicted with aging. In that location is a decrease in vestibulospinal reflexes, and in the power to detect head position and motion in space. These may exist secondary to loss of hair cells and nerve fibers forth with neuronal loss in the medial, lateral, and junior vestibular nucleus in the brainstem. ⁷

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9781416062318100169

Cellular Components of Nervous Tissue

Patrick R. Hof , ... David R. Colman , in From Molecules to Networks, 2004

Retinal Photoreceptors and Cochlear Hair Cells Are Examples of Specialized Sensory Receptors

Retinal photoreceptors and cochlear hair cells are modified neuroepithelial cells that are specialized in the initial transduction of visual and audio-visual stimuli respectively. Comparable specialized neuronal types exist for other sensory modalities, that is, olfactory, gustatory, and vestibular inputs. In contrast, somatosensory inputs are transmitted by peripheral nerve cells whose endings are associated with a variety of sensory structures in the peripheral tissues. Receptor neurons are extremely polarized cells, with i uniquely diversified end that is responsible for the reception of the sensory stimulus. This morphology is especially well demonstrated in retinal photoreceptors. Photoreceptor cells are of 2 types, the rod and the cone, which are specialized for scotopic (low-cal/dark) and color vision, respectively. The rods are slender cells, with an elongated cylindrical outer portion, whereas the cones are smaller elements, with shorter, conical outer portions ( Fig. 1.x) (Krebs and Krebs, 1991). Each cell type consists of an outer segment and an inner segment. The inner segments of both rods and cones contain the metabolic machinery necessary for protein and lipid synthesis and oxidative metabolism. In rods, the outer segment is composed of a very large number of parallel lamellae stacked perpendicularly to the primary centrality of the cylinder. These lamellae are closed, flattened membranous disks that appear in thin-section electron microscopy equally pairs of parallel membranes. In cones, these lamellar stacks are less numerous. These structures are responsible for the mechanisms of phototransduction and contain several visual pigments, located inside the bleary disks, that are necessary for the assimilation of lite.

Cochlear (and vestibular) hair cells also are highly polarized and present hitting upmost differentiation specialized in the detection of endolymphatic movements in the inner ear. In the cochlea, receptor hair cells that find stimuli produced by sound are short, goblet-similar cells embedded in supporting cells (the phalangeal cells of Deiters). Their apical domain contains a U-shaped row of stereocilia (hairs) that are in contact with the tectorial membrane of the organ of Corti. The vibrations of this membrane, generated by sound waves in the endolymph, readapt the hairs and initiate the transduction of the acoustic stimulus. The other pole of the hair cell contains the nucleus and a dumbo population of mitochondria and receives synaptic contacts from afferent and efferent fibers from the cochlear nerve, which spreads around the lower third of the receptor jail cell (Fig. 1.11) (Hudspeth, 1983).

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780121486600500020