Cochlear amplifier

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The cochlear amplifier is a positive feedback mechanism within the cochlea that provides acute sensitivity in the mammalian auditory system. [1] The main component of the cochlear amplifier is the outer hair cell (OHC) which increases the amplitude and frequency selectivity of sound vibrations using electromechanical feedback. [2] [3] [4]

Contents

Discovery

The cochlear amplifier was first proposed in 1948 by Gold. [5] This was around the time when Georg von Békésy was publishing articles observing the propagation of passive travelling waves in the dead cochlea.

Thirty years later the first recordings of emissions from the ear were captured by Kemp. [6] This was confirmation that such an active mechanism was present in the ear. These emissions are now termed otoacoustic emissions and are produced by the cochlear amplifier.

The first modeling effort to define the cochlear amplifier was a simple augmentation of Georg von Békésy's passive traveling wave with an active component. In such a model, a lopsided pressure about the organ of Corti is hypothesized which actively adds to the passive traveling wave to form the active traveling wave. An early example of such a model was defined by Neely and Kim. [7] The existence of otoacoustic emissions is interpreted as implying backward as well as forward traveling waves generated in the cochlea, as proposed by Shera and Guinan. [8]

Contention still surrounds the existence and mechanism of the active traveling wave. Recent experiments [9] show that emissions from the ear occur with such a fast response that the slowly propagating active traveling waves can not explain them. Their explanation for fast emission propagation is the dual of the active traveling wave, the active compression wave. Active compression waves were proposed as early as 1980 by Wilson [10] due to older experimental data. An example model of the active compression wave (pressure wave) is defined by Flax and Holmes. [11]

Other explanations for the active processes in the inner ear exist. [12]

Function

Effect of sound waves on the cochlea

In the mammalian cochlea, wave amplification occurs via the outer hair cells of the organ of Corti. These cells sit directly above a basilar membrane (BM) that has high sensitivity for differences in frequency. Sound waves enter the scala vestibuli of the cochlea and travel throughout it, carrying with them various sound frequencies. These waves exert a pressure on the basilar and tectorial membranes of the cochlea which vibrate in response to sound waves of different frequencies. When these membranes vibrate and are deflected upward (rarefaction phase of sound wave), the stereocilia of the OHCs are deflected toward the tallest stereocilia. This causes the tip links of the OHC hair bundle to open allowing inflow of Na+ and K+ which depolarize the OHC. Upon depolarization, the OHC can then begin its process of amplification through force generated by the hair cell motors.

The somatic motor

The somatic motor is the OHC cell body and its ability to elongate or contract longitudinally due to changes in membrane potential. This function is aptly associated with the OHC structure within the organ of Corti. As seen through scanning electron micrograph imagery, the apical side of the OHC is mechanically coupled to the reticular lamina while the basal side of the OHC is coupled to the Deiter's cell cupula. [13] Because the cell body is not in direct contact with any structure and is surrounded by the fluid-like perilymph, the OHC is considered dynamic and able to support electromotility.

Prestin is the transmembrane protein underlying the OHC's ability to elongate and contract, a process essential for OHC electromotility. This protein is voltage-sensitive. Contrary to previous research, prestin has also been shown to transport anions; the exact role of anion-transport in the somatic motor is still under investigation. [14]

Under resting conditions, it is thought that chloride is bound to allosteric sites in prestin. Upon deflection of the basilar membrane (BM) upwards and subsequent deflection of the hair bundles toward the tallest stereocilia, channels within the stereocilia open allowing the inflow of ions and depolarizing the OHC results. Intracellular chloride dissociates from the allosteric binding sites in prestin, causing contraction of prestin. Upon BM deflection downwards hyperpolarization of the OHC results, and intracellular chloride ions bind allosterically causing prestin expansion. [15] The binding or dissociation of chloride causes a shift in prestin's membrane capacitance. A nonlinear capacitance (NLC) results which leads to a voltage-induced mechanical displacement of prestin into an elongated or contracted state as described above. The larger the voltage nonlinearity, the larger prestin's response; this shows a concentration specific voltage-sensitivity of prestin.

Prestin densely lines the lipid bilayer of the outer hair cell membranes. [14] [15] Therefore, a change in the shape of many prestin proteins, which tend to conglomerate together, will ultimately lead to a change in shape of the OHC. A lengthening of prestin lengthens the hair cell while prestin contraction leads to a decrease in OHC length. [15] Because the OHC is tightly associated with the reticular lamina and the Deiter's cell, shape change of the OHC leads to movement of these upper and lower membranes, causing changes in vibrations detected in the cochlear partition. Upon initial deflection of the BM causing positive hair bundle deflection, the reticular lamina is pushed downward, resulting in a negative deflection of the hair bundles. This causes stereocilia channel closing which leads to hyperpolarization and OHC elongation. [16]

Below the hair bundle is an actin-rich cuticular plate. [13] It has been hypothesized that the role of actin depolymerization is crucial for regulation of the cochlear amplifier. Upon actin polymerization, electromotile amplitude and OHC length increase. [1] These changes in actin polymerization do not alter NLC, showing that actin's role in the cochlear amplifier is separate from that of prestin.

The hair bundle motor

The hair bundle motor is the force generated from a mechanical stimulus. This is done through the use of the mechanoelectrical transduction (MET) channel, which allows for the passage of Na+, K+, and Ca2+. [17] The hair bundle motor operates by deflecting hair bundles in the positive direction and providing positive feedback of the basilar membrane, increasing the movement of the basilar membrane which increases the response to a signal. Two mechanisms have been proposed for this motor: fast adaptation, or channel re-closure, and slow adaptation.

Fast adaptation

This model relies upon a calcium gradient generated by the opening and closing of the MET channel. Positive deflection of the tip links stretches them in the direction of the tallest stereocilia, causing MET channel opening. This allows the passage of Na+, K+, and Ca2+. [18] Additionally, Ca2+ briefly binds to a cytostolic site on the MET channel which is estimated to be only 5 nm from the channel pore. Because of close proximity to the channel opening, it is suspected that Ca2+ binding affinity can be relatively low. When calcium binds to this site, the MET channels begin to close. Channel closure ceases the transduction current and increases the tension in the tip links, forcing them back in the negative direction of the stimulus. Binding of calcium is short-lived, because the MET channel must participate in additional cycles of amplification. When calcium dissociates from the binding site, calcium levels fall rapidly. Due to the differences in calcium concentration at the cytostolic binding site when calcium is bound to the MET channel versus when calcium dissociates, a calcium gradient is created, generating chemical energy. The oscillation of calcium concentration and force generation contributes to amplification. [18] [19] The timecourse of this mechanism is on the order of hundreds of microseconds, which reflects the speed that is necessary for amplification of high frequencies.

Slow adaptation

As opposed to the fast adaptation model, slow adaptation relies on the myosin motor to alter the stiffness of the tip links leading to alterations of channel current. First, the stereocilia are deflected in the positive direction opening the MET channels and allowing for inflow of Na+, K+, and Ca2+. The entering current first increases and then quickly decreases due to myosin's release of tension of the tip link and subsequent closing of channels. [20] It is hypothesized that the tip link is attached to the myosin motor which moves along actin filaments. [21] Again the polymerization of actin could play a crucial role in this mechanism, as it does in OHC electromotility.

Calcium has also been shown to play a crucial role in this mechanism. Experiments have shown that in reduced extracellular calcium, the myosin motor tightens, resulting in more open channels. Then, when additional channels are opened, the inflow of calcium acts to relax the myosin motor, which returns the tip links to their resting state, causing channels to close. [20] This is hypothesized to occur via the binding of calcium to the myosin motor. The timecourse of this event is 10-20 milliseconds. This time scale reflects the time that is needed to amplify low frequencies. [19] Although the largest contributor to slow adaptation is the tension-dependence, calcium-dependence acts as a useful feedback mechanism.

This mechanism of myosin's reaction to hair bundle deflection imparts sensitivity to small changes in hair bundle position.

Integration of electromotility and hair bundle dynamics

Electromotility of the OHC by prestin modulation produces significantly larger forces than the forces generated by deflection of the hair bundle. One experiment showed that the somatic motor produced a 40-fold greater force at the apical membrane and a sixfold greater force at the basilar membrane than the hair bundle motor. The difference in these two motors is that there are different polarities of hair bundle deflection for each motor. The hair bundle motor uses a positive deflection leading to a generation of force, while the somatic motor uses negative deflection to generate force. However, both the somatic motor and the hair bundle motor produce significant displacements of the basilar membrane. This, in turn, leads to augmentation of bundle movement and signal amplification. [16]

The mechanical force that is generated by these mechanisms increases the movement of the basilar membrane. This, in turn, influences the deflection of the hair bundles of the inner hair cells. These cells are in contact with afferent fibers that are responsible for transmitting signals to the brain.

Related Research Articles

<span class="mw-page-title-main">Inner ear</span> Innermost part of the vertebrate ear

The inner ear is the innermost part of the vertebrate ear. In vertebrates, the inner ear is mainly responsible for sound detection and balance. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:

<span class="mw-page-title-main">Cochlea</span> Snail-shaped part of inner ear involved in hearing

The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory organ of hearing, which is distributed along the partition separating the fluid chambers in the coiled tapered tube of the cochlea.

<span class="mw-page-title-main">Basilar membrane</span>

The basilar membrane is a stiff structural element within the cochlea of the inner ear which separates two liquid-filled tubes that run along the coil of the cochlea, the scala media and the scala tympani. The basilar membrane moves up and down in response to incoming sound waves, which are converted to traveling waves on the basilar membrane.

<span class="mw-page-title-main">Organ of Corti</span> Receptor organ for hearing

The organ of Corti, or spiral organ, is the receptor organ for hearing and is located in the mammalian cochlea. This highly varied strip of epithelial cells allows for transduction of auditory signals into nerve impulses' action potential. Transduction occurs through vibrations of structures in the inner ear causing displacement of cochlear fluid and movement of hair cells at the organ of Corti to produce electrochemical signals.

<span class="mw-page-title-main">Auditory system</span> Sensory system used for hearing

The auditory system is the sensory system for the sense of hearing. It includes both the sensory organs and the auditory parts of the sensory system.

<span class="mw-page-title-main">Hair cell</span> Auditory sensory receptor nerve cells

Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment.

<span class="mw-page-title-main">Sensorineural hearing loss</span> Hearing loss caused by an inner ear or vestibulocochlear nerve defect

Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ or the vestibulocochlear nerve. SNHL accounts for about 90% of reported hearing loss. SNHL is usually permanent and can be mild, moderate, severe, profound, or total. Various other descriptors can be used depending on the shape of the audiogram, such as high frequency, low frequency, U-shaped, notched, peaked, or flat.

In physiology, tonotopy is the spatial arrangement of where sounds of different frequency are processed in the brain. Tones close to each other in terms of frequency are represented in topologically neighbouring regions in the brain. Tonotopic maps are a particular case of topographic organization, similar to retinotopy in the visual system.

<span class="mw-page-title-main">Stereocilia (inner ear)</span>

In the inner ear, stereocilia are the mechanosensing organelles of hair cells, which respond to fluid motion in numerous types of animals for various functions, including hearing and balance. They are about 10–50 micrometers in length and share some similar features of microvilli. The hair cells turn the fluid pressure and other mechanical stimuli into electric stimuli via the many microvilli that make up stereocilia rods. Stereocilia exist in the auditory and vestibular systems.

<span class="mw-page-title-main">Mechanotransduction</span> Conversion of mechanical stimulus of a cell into electrochemical activity

In cellular biology, mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception, touch, balance, and hearing. The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals.

<span class="mw-page-title-main">Prestin</span>

Prestin is a protein that is critical to sensitive hearing in mammals. It is encoded by the SLC26A5 gene.

<span class="mw-page-title-main">Motor protein</span> Class of molecular proteins

Motor proteins are a class of molecular motors that can move along the cytoplasm of animal cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.

<span class="mw-page-title-main">Tectorial membrane</span>

The tectoria membrane (TM) is one of two acellular membranes in the cochlea of the inner ear, the other being the basilar membrane (BM). "Tectorial" in anatomy means forming a cover. The TM is located above the spiral limbus and the spiral organ of Corti and extends along the longitudinal length of the cochlea parallel to the BM. Radially the TM is divided into three zones, the limbal, middle and marginal zones. Of these the limbal zone is the thinnest (transversally) and overlies the auditory teeth of Huschke with its inside edge attached to the spiral limbus. The marginal zone is the thickest (transversally) and is divided from the middle zone by Hensen's Stripe. It overlies the sensory inner hair cells and electrically-motile outer hair cells of the organ of Corti and during acoustic stimulation stimulates the inner hair cells through fluid coupling, and the outer hair cells via direct connection to their tallest stereocilia.

A kinocilium is a special type of cilium on the apex of hair cells located in the sensory epithelium of the vertebrate inner ear.

The neural encoding of sound is the representation of auditory sensation and perception in the nervous system.

Auditory fatigue is defined as a temporary loss of hearing after exposure to sound. This results in a temporary shift of the auditory threshold known as a temporary threshold shift (TTS). The damage can become permanent if sufficient recovery time is not allowed before continued sound exposure. When the hearing loss is rooted from a traumatic occurrence, it may be classified as noise-induced hearing loss, or NIHL.

Electrocochleography is a technique of recording electrical potentials generated in the inner ear and auditory nerve in response to sound stimulation, using an electrode placed in the ear canal or tympanic membrane. The test is performed by an otologist or audiologist with specialized training, and is used for detection of elevated inner ear pressure or for the testing and monitoring of inner ear and auditory nerve function during surgery.

<span class="mw-page-title-main">Tip link</span>

Tip links are extracellular filaments that connect stereocilia to each other or to the kinocilium in the hair cells of the inner ear. Mechanotransduction is thought to occur at the site of the tip links, which connect to spring-gated ion channels. These channels are cation-selective transduction channels that allow potassium and calcium ions to enter the hair cell from the endolymph that bathes its apical end. When the hair cells are deflected toward the kinocilium, depolarization occurs; when deflection is away from the kinocilium, hyperpolarization occurs. The tip link is made of two different cadherin molecules, protocadherin 15 and cadherin 23. It has been found that the tip links are relatively stiff, so it is thought that there has to be something else in the hair cells that is stretchy which allows the stereocilia to move back and forth.

Peter Dallos is the John Evans Professor of Neuroscience Emeritus, Professor Emeritus of Audiology, Biomedical Engineering and Otolaryngology at Northwestern University. His research pertained to the neurobiology, biophysics and molecular biology of the cochlea. This work provided the basis for the present understanding of the role of outer hair cells in hearing, that of providing amplification in the cochlea. After his retirement in 2012, he became a professional sculptor.

<span class="mw-page-title-main">A. James Hudspeth</span>

A. James Hudspeth is the F.M. Kirby Professor at Rockefeller University in New York City, where he is director of the F.M. Kirby Center for Sensory Neuroscience. His laboratory studies the physiological basis of hearing.

References

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  2. ↑ Ashmore, Jonathan Felix (1987). "A fast motile response in guinea-pig outer hair cells: the cellular basis of the cochlear amplifier". The Journal of Physiology . 388 (1): 323–347. doi:10.1113/jphysiol.1987.sp016617. ISSN   1469-7793. PMC   1192551 . PMID   3656195. Open Access logo PLoS transparent.svg
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  5. ↑ T. Gold 1948 : Hearing. II. The Physical Basis of the Action of the Cochlea
  6. ↑ D. T. Kemp 1978 : Stimulated acoustic emissions from within the human auditory system
  7. ↑ Neely, S. T. and Kim, D. O., 1986. A model for active elements in cochlear biomechanics. The Journal of the Acoustical Society of America, 79(5), pp. 1472–1480.
  8. ↑ Shera, C. A. and Guinan, J. J. Jr., 1999. Evoked otoacoustic emissions arise by two fundamentally different mechanisms: a taxonomy for mammalian OAEs. The Journal of the Acoustical Society of America, 105(2), pp. 782–798.
  9. ↑ Ren, T., He, W., Scott, M. and Nuttall, A. L., 2006. Group delay of acoustic emissions in the ear. Journal of Neurophysiology, 96(5), pp. 2785–2791.
  10. ↑ Wilson, J.P., 1980. Evidence for a cochlear origin for acoustic re-emissions, threshold fine-structure and tonal tinnitus. Hearing Research, 2(3–4), pp. 233–252.
  11. ↑ Flax, M. R., & Holmes, W. H. (2011, November). A mixed mode cochlear amplifier including neural feedback. In AIP Conference Proceedings (Vol. 1403, No. 1, pp. 611-617). American Institute of Physics.
  12. ↑ e.g.: Bell, A. and Fletcher, N. H., 2004. The cochlear amplifier as a standing wave: "Squirting" waves between rows of outer hair cells?. The Journal of the Acoustical Society of America, 116(2), pp. 1016–1024.
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  14. 1 2 Bai, J. P.; Surguchev, A.; Montoya, S.; Aronson, P. S.; Santos-Sacchi, J.; Navaratnam, D. (2009). "Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent". Biophysical Journal. 96 (8): 3179–3186. Bibcode:2009BpJ....96.3179B. doi:10.1016/j.bpj.2008.12.3948. PMC   2718310 . PMID   19383462.
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  17. ↑ Sul, B.; Iwasa, K. H. (2009). "Effectiveness of Hair Bundle Motility as the Cochlear Amplifier". Biophysical Journal. 97 (10): 2653–2663. Bibcode:2009BpJ....97.2653S. doi:10.1016/j.bpj.2009.08.039. PMC   2776295 . PMID   19917218.
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  21. ↑ Howard, J.; Hudspeth, A. J. (1987). "Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell". Proceedings of the National Academy of Sciences of the United States of America. 84 (9): 3064–3068. Bibcode:1987PNAS...84.3064H. doi: 10.1073/pnas.84.9.3064 . PMC   304803 . PMID   3495007.
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