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Hearing and balance are very different senses functionally, but they begin peripherally in very similar ways. The eighth cranial nerve carries two special sensory components, one in a cochlear division and one in a vestibular division. Both divisions innervate elaborate end-organs containing specialized mechanoreceptors (called hair cells because of their appearance), but accessory structures in the end-organs specialize the two divisions to respond to different types of mechanical stimuli. The cochlear division carries information about sound, whereas the vestibular division signals position and movement of the head.
The structures innervated by the eighth cranial nerve are embedded in the temporal bone ( Figs. 14.1 and 14.2 ), where the receptor cells form parts of the walls of a convoluted, membranous tube that is suspended within the bony structure of the temporal bone ( Fig. 14.3 ).
The walls of the bony structure are formed by the hardest bone in the body—the petrous (“like a rock”) portion of the temporal bone. Because the structure consists of so many twists and turns, it is called the bony labyrinth. The coiled cochlea (Latin for “snail shell”) extends anteriorly from an enlargement called the vestibule, to which three semicircular canals are attached. The membranous labyrinth, the membranous tube suspended within the bony labyrinth, generally follows the same contours (see Fig. 14.3 ). Therefore there is a cochlear duct within the bony cochlea and a semicircular duct within each semicircular canal. However, the vestibule contains two enlargements of the membranous labyrinth, the utricle (to which the semicircular ducts attach) and the saccule (which is connected to the cochlear duct and to the utricle).
The bony labyrinth is filled with perilymph, which is similar in composition to cerebrospinal fluid (CSF) and therefore to extracellular fluid generally (i.e., low K + concentration and high Na + concentration—about 5 and 140 mM, respectively). The subarachnoid space around the brain is actually continuous with the perilymphatic space of the bony labyrinth through a tiny canal in the temporal bone (the cochlear aqueduct). The membranous labyrinth, in contrast, is filled with endolymph, a very peculiar fluid that is more like intracellular fluids in ionic composition (K + concentration about 150 mM, Na + concentration about 1 to 2 mM). As may be expected from this difference in fluid composition, the membranous labyrinth is a continuous, closed system in which every part communicates with every other part (like CSF in the ventricles). A system of tight junctions joins some cells in the walls of the membranous labyrinth, forming a diffusion barrier between endolymph and perilymph. The receptor cells of the labyrinth (hair cells) form part of this diffusion barrier; as discussed later in this chapter, the resulting voltage and concentration gradients across parts of their membranes are important in the transduction process.
Endolymph is produced continuously by specialized epithelial cells called stria vascularis in one wall of the cochlear duct and in several other locations in the membranous labyrinth, using an active pumping mechanism that results in a positive electrical potential inside the membranous labyrinth. Endolymph seems to have a path of circulation and reabsorption reminiscent of that of CSF. The semicircular ducts communicate with the utricle, and the cochlear duct communicates with the saccule. The ducts interconnecting the utricle and saccule meet in a Y -shaped junction through which endolymph can enter the endolymphatic duct, leave the labyrinth, and reach the endolymphatic sac in the dura covering the temporal bone, where some of it is reabsorbed. Just as obstruction of CSF flow causes expansion of the ventricles and neurological symptoms, obstruction of endolymph flow was naturally thought to cause ballooning of the membranous labyrinth and otological symptoms ( Clinical Focus Box 14.1 ).
Meniere's disease is characterized by transient attacks of vertigo, nausea, and hearing loss accompanied by ringing in the ears (tinnitus). Approximately 100,000 patients develop Meniere's disease every year. Meniere's disease tends to be more prevalent in females, and the mean age at diagnosis is at 55 years. Its defining anatomical feature is swelling of the membranous labyrinth (referred to as endolymphatic hydrops), usually attributed to endolymphatic blockage. The abnormal increase in the volume and pressure of the endolymph fluid can cause progressive degeneration of the specialized hair cells of the vestibular and cochlear apparatus. Some cases of hydrops are asymptomatic, however, and there are occasional cases of patients with Meniere's symptoms but no hydrops. Although there are probably multiple causes of Meniere's disease, in many cases the hydrops is likely to be a secondary result of some still unknown process that disrupts fluid secretion in the membranous labyrinth and damages hair cells. In most individuals with Meniere's disease, the cause is unknown, although there are some rare familial forms of Meniere's disease reported.
Diagnosis includes patients having sudden attacks of dizziness (vertigo) that may last a few hours and subside gradually. The attacks may be associated with nausea and vomiting. The patient may have a recurrent feeling of fullness or pressure in the affected ear, and hearing tends to fluctuate. Over the years hearing may progressively worsen. Tinnitus may be constant or intermittent and can affect one ear (most often) or both ears (10% to 15%).
Certain medications, such as antihistamines or the anticholinergic medication scopolamine, may alleviate symptoms of vertigo. During an episode a patient may want to remain seated to prevent falls, and at times patients may need medications to relieve nausea and vomiting. Surgery is available in severe cases.
Hair cells of the labyrinth were named for the array of a hundred or so specialized microvilli that project as a bundle from one end of the cell into the endolymphatic interior of the membranous labyrinth ( Fig. 14.4 ); the other end of each hair cell synapses on peripheral processes of eighth nerve fibers, which in turn convey auditory and vestibular information to the central nervous system (CNS). Hair cell microvilli, somewhat illogically referred to as stereocilia, are arranged asymmetrically: they are lined up in graduated rows, so the tallest are toward one side of the hair cell. Adjacent to the tallest stereocilia of each hair cell in the semicircular ducts, utricle, and saccule is a single true cilium, the kinocilium. Cochlear hair cells have kinocilia that degenerate during fetal development, indicating that these processes play no essential role in the transduction process; kinocilia may instead be important for establishing the anatomical asymmetry of hair cells or for some mechanical connections of the hair cells in which they persist.
Hair cells are grouped into six discrete clusters in different parts of the labyrinth ( Table 14.1 ; see also Fig. 14.3 ), and fundamental aspects of the arrangement of each cluster are the same. The stereocilia of the hair cells (and the kinocilium, when present) protrude into the endolymphatic space inside the membranous labyrinth, where the tips of the kinocilium and the tallest stereocilia are usually embedded in a specialized mass of gelatinous material, one for each cluster of hair cells. Movement of the gelatinous mass relative to the hair cells causes deflection of stereocilia, which in turn causes a receptor potential through a transduction mechanism described later.
Location of Hair Cells | Part of Labyrinth | Gelatinous Material | Stimulus Transduced |
---|---|---|---|
Organ of Corti | Cochlea | Tectorial membrane | Sound |
Cristae | Semicircular ducts | Cupula | Angular acceleration |
Maculae | Utricle, saccule | Otolithic membrane | Linear acceleration |
In sections through the labyrinth (see Fig. 14.9 ), hair cells and associated structures often appear to be bathed in the endolymph that fills the membranous labyrinth. If this were the case, however, eighth nerve fibers reaching the bases of hair cells would also be passing through endolymph. Endolymph has such a high K + concentration that standard nerve fibers could not work in its presence. In fact, the real barrier between endolymph and perilymph is a series of tight junctions near the tops of the hair cells, between the hair cells and neighboring supporting cells. Because perilymph is continuous with the CSF of subarachnoid space, marker substances introduced into cisterna magna infiltrate the sensory epithelia of the labyrinth and surround the hair cells, stopping only at the array of tight junctions ( Fig. 14.5 ). Therefore the stereocilia and the apical surfaces of hair cells are exposed to endolymph, whereas other surfaces of the hair cells, and the nerve fibers they contact, are bathed in perilymph (see Fig. 14.9E ).
Stereocilia are packed full of cross-linked actin filaments (see Fig. 14.6C ), which makes them rigid. In response to mechanical deformation they do not bend but rather pivot at their bases, where they are attached to the hair cell. Various linking molecules interconnect neighboring stereocilia, so the whole hair bundle moves as a unit in response to mechanical stimuli. Some of these links are symmetrical, connecting a given stereocilium to all of its neighbors. In addition, fine filamentous connections called tip links extend from the tip of each stereocilium to its next tallest neighbor ( Fig. 14.6 ). Tip links have a special role in the transduction process, which (at least in a conceptual sense) is remarkably straightforward ( Fig. 14.7 ). A mechanically gated cation channel is located at one or both ends of each tip link and is normally open part of the time. Deflecting the hair bundle toward the tallest stereocilia stretches the tip links, increasing the probability of channel opening. The channels are permeable to most small cations, and because K + ions are the most abundant cations in endolymph, they flow down the electrical gradient from the positive endolymph into the negative interior of the hair cells. The resulting inward K + current depolarizes the hair cells, a
a Increased K + conductance in typical neurons causes K + efflux and hyperpolarization, reflecting the fact that the K + equilibrium potential is typically around −90 mV. However, because of the high K + concentration in endolymph, the K + equilibrium potential across the membranes of stereocilia is about 0 mV.
causing the opening of voltage-gated Ca 2+ channels and increased release of transmitter onto eighth nerve endings. The excitatory transmitter (probably glutamate) then causes an increased firing frequency in the eighth nerve fibers. Deflecting the hair bundle in the opposite direction decreases the tension on the tip links; the transduction channels close, baseline K + current stops, the hair cells hyperpolarize, and transmitter release and firing rate diminish. Deflecting the hair bundle in a perpendicular direction (i.e., parallel to the rows of stereocilia) has no effect on the tip links and so does not cause a receptor potential.
Hair cells in all parts of the labyrinth use the same basic transduction mechanism, initiated by movement of a gelatinous mass and deflection of stereocilia. The critical variable in different parts of the labyrinth is the physical coupling between the gelatinous masses and the stereocilia. This is the key: variations in the way these gelatinous masses are made up and arranged, and the way different parts of the membranous labyrinth are suspended mechanically, set up some hair cells to respond to sound, others to head movement, and still others to head position.
The auditory system faces a basic mechanical problem: the sound vibrations that it must detect are propagated in air, whereas the auditory receptor cells (like other elements of the nervous system) live in a fluid-filled environment. Water is harder to move than air, and nearly all the sound energy incident on a simple air-water interface is reflected. Fluids in small channels like the labyrinth are even harder to move, with the result that if the auditory receptor organ (the organ of Corti ) and its fluid surroundings were mechanically coupled to the outside world by a simple membrane, it would receive no more than 0.1% of the sound energy that fell on the membrane. One major task of the air-filled outer and middle ears (see Fig. 14.1 ) is therefore to transfer sound as efficiently as possible to the fluid-filled inner ear.
The outer ear is basically a complicated funnel consisting of the auricle (or pinna ) and the external auditory meatus or canal; it conducts sound to the tympanic membrane. Sound-induced vibrations are then transferred along a chain of three small bones, or ossicles, that traverse the middle ear cavity (an air-filled cavity in the temporal bone). The handle of the malleus is attached to the medial surface of the tympanic membrane, so movements of this membrane are transferred directly to the malleus. The malleus in turn is attached to the incus, which is attached to the stapes, so sound-induced vibrations eventually reach the oval-shaped footplate of the stapes. The footplate of the stapes occupies a hole in the temporal bone called the oval window; on the other side of the oval window is the perilymph-filled vestibule of the bony labyrinth. The vestibule leads directly to the cochlea, which contains the organ of Corti. Thus vibration of the tympanic membrane ultimately results in movement of the fluids of the inner ear.
The chain of middle ear ossicles acts as a lever system with a small mechanical advantage, so a given force at the tympanic membrane results in a slightly greater force at the footplate of the stapes. More importantly, the active, or moving, area of the tympanic membrane is about 15 times that of the footplate of the stapes. The net result of the mechanical advantage and the size difference is that stapedial vibrations have a much greater force per unit area of the footplate; this force is sufficient to move the perilymph, and more than 60% of the sound energy incident on the tympanic membrane is successfully transferred to the inner ear. Therefore the middle ear apparatus acts as a transformer, much as an electrical transformer alters the voltage and current of a source to better match the requirements of a particular circuit. The effectiveness of this system is extraordinary. At a threshold of 3000 Hz (the frequency to which we are most sensitive) the tympanic membrane moves a distance somewhat less than the diameter of a single hydrogen atom. b
b This is as sensitive as an ear can usefully be made. Under ideal conditions in a very quiet setting, blood can be heard flowing through the vessels near the ear. If ears were much more sensitive, we would be distracted by hearing noise generated by air molecules colliding with the tympanic membrane.
By the time such a threshold vibration of the tympanic membrane reaches the cochlear hair cells, it deflects their stereocilia through an angle of only about 0.003 degree. Bending the Empire State Building through an angle of 0.003 degree would deflect its top by less than an inch. c
c An Americanization of an Eiffel Tower analogy presented by A. J. Hudspeth in Nature 341:397, 1989.
From this threshold we can hear over a 10 million–fold range of sound pressure levels before sounds become painfully loud. (Because it is cumbersome to keep track of all the zeros in such large numbers, a logarithmic decibel scale, as described in Box 14.1 , is used to express sound pressure levels.) In addition, although human hearing is most sensitive at about 3000 Hz, the frequency range of human hearing in healthy young adults extends from about 20 to 20,000 Hz ( Fig. 14.8 ). All this is accomplished with a surprisingly small number of nerve fibers: in contrast to the million or so axons in an optic nerve, there are only about 30,000 fibers in a human cochlear nerve. Somehow, the CNS analyzes the information carried by these 30,000 fibers, enabling us to detect and interpret the myriad sounds of nature, music, and human language.
Because the range of sound levels over which we have useful hearing is so vast, a logarithmic scale has been devised to indicate the volume of one sound relative to some standard. The unit in this scale as originally defined is the bel, named for Alexander Graham Bell, the inventor of the telephone:
where I is the intensity of the sound in question and I 0 is a reference intensity (usually the threshold for normal hearing).
Bels are big units, representing large changes in sound intensities, so tenths of bels, or decibels (dB), are used instead:
In practice, it is much easier to measure the pressure level of a sound than its intensity. Because intensity is proportional to the square of the pressure, decibels are 20 times the log of the pressure ratio (seemingly contrary to the implication of the term deci bel):
where P is the pressure of the sound in question and P 0 is a reference pressure (usually the threshold for normal hearing).
So a sound pressure level 10 million times greater than threshold is 140 dB above threshold (see Fig. 14.8 ):
Multiple mechanical properties of the outer, middle, and inner ears collaborate to determine the sensitivity of ears to sounds of various frequencies. The combined result of all these factors is that we are most sensitive in the 1000- to 3000-Hz range important for spoken language, somewhat less sensitive at higher frequencies, and much less sensitive at lower frequencies (see Fig. 14.8 ).
Two tiny muscles attached to the middle ear bones modulate the transmission of vibrations to the inner ear. One, the tensor tympani, is attached to the handle of the malleus; when it contracts, it increases the tension on the tympanic membrane and decreases the transmission of vibrations through the ossicular chain. The other muscle, the stapedius, is attached to the neck of the stapes; it too decreases the transmission of vibrations when it contracts. The tensor tympani receives motor innervation from the trigeminal nerve and the stapedius from the facial nerve; both muscles are involved in certain auditory reflexes (described later).
The auditory part of the inner ear, like the vestibular part, consists of a portion of the endolymph-filled membranous labyrinth suspended within a portion of the perilymph-filled bony labyrinth.
The bony part is the cochlea, which coils through turns from its relatively broad base to its apex. (The cochlea lies on its side in the temporal bone, with its base facing medially and posteriorly [see Fig. 14.26 ], but for the sake of simplicity, it is usually discussed as though it sits upright on its base.) The cochlea has a core of spongy bone called the modiolus, from which the osseous spiral lamina projects like the threads of a screw ( Fig. 14.9 ). A winding cavity within the modiolus parallels the spiral lamina and houses the spiral ganglion, which contains the cell bodies of the auditory primary afferent fibers. The central processes of these cells collect at the base of the cochlea to form the cochlear division of the eighth nerve; the peripheral processes pass in bundles through a series of canals in the osseous spiral lamina to innervate the auditory receptors.
The cochlear duct (the auditory portion of the membranous labyrinth) is firmly anchored to the bony labyrinth in such a way that the duct is triangular in cross section (see Fig. 14.9C ). One corner of the triangle is attached to the osseous spiral lamina, and the other two corners are attached to the outer wall of the bony cochlea. The result is that the cochlear duct and osseous spiral lamina act as a partition between two perilymphatic spaces (except at the apex of the cochlea, where perilymph can pass from one space to the other through a small opening called the helicotrema [Greek for “the hole in the spiral”]). The perilymphatic space above the cochlear duct is called scala vestibuli because it is directly continuous with the perilymph of the vestibule. The space below the cochlear duct is called scala tympani because it ends blindly at the round window membrane (also called the secondary tympanic membrane ). The space enclosed by the cochlear duct is filled with endolymph and is called scala media. Each of the three walls of the cochlear duct has a different structure (see Fig. 14.9D ). The thin vestibular (or Reissner's ) membrane borders scala vestibuli and probably serves mainly as a diffusion barrier between the endolymph and perilymph, playing no great role in the mechanical properties of the cochlea. The spiral ligament, thickened periosteal tissue adhering to the inner surface of the bony cochlea, forms the second wall. It includes on its endolymph-facing surface the stria vascularis, a specialized secretory epithelium that produces most of the endolymph in the membranous labyrinth. Finally, the basilar membrane spans the gap between the edge of the osseous spiral lamina and the spiral ligament, completing the “floor” of the cochlear duct and separating scala media from scala tympani.
Vibrations reaching the stapes footplate are transferred to the perilymph of the vestibule, adjacent to scala vestibuli. Although perilymph is incompressible, the round window membrane is elastic, allowing these vibrations to enter the labyrinth. When the stapes footplate moves inward, the round window membrane bulges out; when the footplate moves outward, the membrane is drawn inward. In the process, small quantities of perilymph are displaced within the cochlea. Most of this energy passes directly from scala vestibuli to scala tympani, deforming the cochlear duct ( Fig. 14.10 ). The cochlear duct contains the auditory receptors, and this deformation stimulates some of them. Static pressure changes and vibrations of very low frequency simply move a little perilymph through the helicotrema and do not deform the cochlear duct.
Three basic parameters that must be encoded by the auditory system during its initial analysis of a sound are the intensity, frequency, and location of the stimulus. The intensity of a sound, like intensity in other sensory systems, is coded by the rate of action potential firing in populations of nerve fibers and by the numbers of nerve fibers responding. Frequency is indicated largely by the particular part of the organ of Corti that is most active, through a mechanism described shortly. Analysis of the location of a sound, as discussed later in this chapter, depends heavily on a comparison of sounds reaching the two ears and so is accomplished in the CNS.
The organ of Corti ( Figs. 14.11 and 14.12 ) is a strip of hair cells and supporting cells about 35 mm long that rests on the basilar membrane. The hair cells are arranged in two groups: a single row of about 3500 inner hair cells near the edge of the osseous spiral lamina and a band of about 15,000 outer hair cells three to five cells wide, directly above the flexible basilar membrane. The two groups are separated by a perilymphatic space called the tunnel of Corti, through which the peripheral processes of eighth nerve fibers must pass on their way to the outer hair cells. The stereocilia of the outer hair cells are inserted into the gelatinous tectorial membrane, so vibration of the basilar membrane causes oscillations of the hairs and therefore oscillation of the membrane potential of the hair cells. The stereocilia of the inner hair cells, in contrast, are not attached to the tectorial membrane; these hair cells apparently are stimulated directly by endolymph squirting back and forth through the narrow space between their tops and the tectorial membrane.
A pressure pulse delivered to scala vestibuli by movement of the stapes causes a traveling wave of deformation to move along the basilar membrane ( Fig. 14.13A and B ), much as waves spread from the site of a pebble dropped into a body of water. However, because the mechanical properties of the basilar membrane vary progressively along its length, the traveling wave reaches its peak amplitude at a location that depends on the frequency of the stimulus. The basilar membrane is about 100 µm wide and relatively stiff at the base of the cochlea, and about 500 µm wide and relatively floppy at the apex (see Fig. 14.11 , inset ). The entire basilar membrane, from the base to the apex of the cochlea, responds to intense low-frequency sounds, but closer to threshold it is driven most effectively by sounds of progressively higher frequencies as one moves from the apex to the base of the cochlea (see Fig. 14.13C ). Because the organ of Corti (which contains the auditory receptor cells) rests on the basilar membrane, different receptor cells respond best to sounds of different frequencies. d
d Low frequencies vibrate large extents of the basilar membrane and additional information about low frequencies is provided by multiple eighth nerve fibers all firing in phase with the sound wave.
Individual eighth nerve fibers respond to a broad range of frequencies when the sound is intense but are sharply tuned to a narrow range of frequencies at threshold (see Fig. 14.15 ). This mechanical tuning of the basilar membrane is the beginning of a tonotopic organization within the auditory system, analogous to the somatotopic organization of the somatosensory system and the retinotopic organization of the visual system; in this case, particular frequencies are mapped in an orderly fashion onto particular areas of relay nuclei and auditory cortex of the temporal lobe (see Fig. 14.19 ). Cochlear implants take advantage of this tonotopic organization of the basilar membrane and its overlying hair cells ( Clinical Focus Box 14.2 ).
Hearing loss occurs gradually with age, called presbycusis, and is the common result of the gradual loss of hair cells in the cochlea. About one-third of people in the United States between the ages of 65 and 75 have some degree of hearing loss. Hearing loss can be defined as one of two types: conductive, which involves outer or middle ear not allowing the air wave to transmit to the inner ear, and, sensorineural, which involves damage to the inner ear (e.g., damage to the hair cells, cochlear nerve fibers, or the cochlear nuclei) (see Fig. 14.22B and C ).
Causes of conductive hearing loss include the gradual buildup of earwax or an ear infection that can block the ear canal and prevent conduction of sound waves, as well as abnormal bone growths or tumors of the middle ear, impairing proper bone ossicle function. Additional causes of conductive hearing loss include ruptured eardrum (e.g., tympanic membrane perforation), loud blasts of noise, and sudden changes in pressure.
Factors that may cause sensorineural loss that are due to damage to the hair cells and/or cochlear nerve in the inner ear include degeneration of inner ear structures over time, loud noises causing damage to the hair cells, heredity, and some medications including certain antibiotics (e.g., gentamicin, streptomycin, neomycin), sildenafil, and select chemotherapeutics (cyclophosphamide, cisplatin, bleomycin). Temporary effects can cause tinnitus and/or hearing loss, including very high doses of aspirin, other nonsteroidal antiinflammatory drugs, antimalarial drugs, or loop diuretics. A tumor in the peripheral nervous system or central nervous system (CNS) may also affect hearing. A common type of tumor called a schwannoma affects cranial nerve VIII function before the nerve enters the CNS and can result in hearing and balance impairment.
Therefore hearing loss measured by air conduction could be the result of damage at any site in from the outer ear to the inner ear or the pathways to the cortex. Hearing loss by bone conduction, in contrast, involves direct transmission of vibrations from the skull to the fluids of the inner ear, bypassing the outer and middle ears.
The diagnosis of hearing loss includes performing a physical exam and observation of the ear for a possible conduction block such as earwax or inflammation from an infection. Using a tuning fork for the sound of the tuning fork and the vibration on the temporal bone can help determine whether there is a conduction or sensorineural problem. Audiometer tests can be performed as well.
Treatments for hearing loss, depending on the type of loss, can include removing wax blockage or treating the infection/inflammation. If repeated infections with persistent fluid occur, a small tube can be inserted surgically that helps the ears drain. Surgical procedures can be performed in the cases of abnormalities of the eardrum or bones of hearing (ossicles). Hearing aids, which amplify the air-wave signal, are common with aging and loss of hair cells.
Cochlear implants are surgically placed for more severe hearing loss in the case of severe damage to the cochlear hair cells or in cases of congenital development. With cochlear implants an array of electrodes are threaded through the round window membrane and into scala tympani, so different electrodes in the array are located near different points along the basilar membrane. A small microphone and associated electronics can then be used to analyze the sound frequencies of auditory stimuli, break them down into different frequency bands, and stimulate endings of eighth nerve fibers at tonotopically appropriate levels. In many cases, such direct stimulation of cochlear nerve fibers makes nearly normal speech perception possible.
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