Cochlea

COCHLEA
Form and ultrastructure

By
Dr. Syed Salman Hussaini
P.G. 1st Year
Department of ENT
Al-Ameen Medical College, Bijapur


Situated in the inner ear and consists of a spiral tubular
duct embedded in the petrous bone, lined by membranes.

Membraneous compartments are filled with fluid and open
into the vestibule of the inner ear at the cochlear base.

Two membrane-covered openings in the bone at the base
of the spiral, the oval and round windows.

The oval window membrane is attached to the stapes,
through which sound pressure waves enter the cochlear
fluids.

The round window functions to release the pressure
induced by sound stimulation in the incompressible internal
fluids preventing rupture of the internal membranes.

Pressure waves caused by sound travel through the cochlea
They are analysed by a complex and delicate sensory
epithelium situated within the cochlear duct, the organ of
Corti.
The basic function of the organ of Corti is to transduce and
process sound stimuli, converting them into electrical
signals in the auditory nerve for transmission to the higher
auditory pathway.
The stimulus is also analysed for frequency content and
amplitude, both properties being encoded in the individual
and ensemble discharge patterns of auditory nerve fibres.

ULTRASTRUCTURE OF
THE COCHLEA

Structure of the cochlear duct

The cochlear duct is subdivided by two longitudinally
running membranes that separate three chambers, the
scala tympani, scala media and scala vestibuli.

The organ of Corti runs in a spiral along the floor of the
scala media, situated on its lower boundary, an acellular
layer called the basilar membrane.

The scala media is triangular in section, the other
boundaries represented by Reissner's membrane, which
runs obliquely with respect to the basilar membrane from a
ridge of tissue, the spiral limbus near the modiolus, to
the lateral wall that runs along the inside of the bony wall.


The basilar membrane stretches across the cochlear duct
from a bony shelf spiralling around the central bony
modiolus , the osseous spiral lamina, to a bony
promontory, the spiral prominence, on the inside of the
outer wall of the cochlea.

Although the cochlear duct widens substantially towards the
basal end of the spiral, the width of the basilar membrane
decreases, the difference being accounted for by the more
rapidly increasing width of the osseous spiral lamina.

The organ of Corti extends across the upper surface of the
basilar membrane from the spiral limbus situated over the
osseous spiral lamina to the Claudius' cells that lie
between the edge of the sensory region and the outer
anchorage of the basilar membrane.


Underneath the basilar membrane is a layer of
spindleshaped cells, the tympanic cells, whose long axes
are orientated in an apical-basal direction along the
cochlea.

A branching spiral vessel lies under the basilar membrane.


The longitudinal ridge of the spiral limbus is composed of a layer
of epithelial cells, the interdental cells, forming its upper
surface and a main body containing blood vessels and
connective tissue cells embedded in extracellular matrix.

The side of the limbus facing the organ of Corti is concave. The
concavity is lined by cells and forms a longitudinal groove, called
the inner sulcus, which borders the region of the organ of Corti
containing the sensory cells and the supporting cells.

An acellular flap, the tectorial membrane forms a thin layer
over the weakly convex top of the spiral limbus and projects over
the inner sulcus and across the organ of Corti.

It widens substantially in cross sectional area as it does so, to a
maximum, then tapers again to a thin edge that lies over the
outer side of the organ of Corti.


Reissner's membrane consists of two layers of cells
separated by a basement membrane.

The layer facing into the scala tympani is the mesothelial
cell layer and consists of cells with an extremely thin
cytoplasm and prominent central nucleus.

Facing the scala media is the endothelial cell layer,
consisting of a greater density of thicker cells covered by a
dense mat of microvilli.

The cells within each layer are joined by tight junctions
which act as an impermeable barrier to ions and small
molecules.


The lateral wall consists of the stria vascularis,
composed of three layers of cells on the external side of
which is a layer of fibrocytes and connective tissue called
the spiral ligament.

Both regions are supplied with blood vessels.

The three layers of the stria vascularis are composed of
marginal cells facing the scala media, the intermediate
cells and the basal cells.

Intermediate cells tend to have highly convoluted
membranes.

The marginal cells also have tight junctions connecting
them together.


The cells of the lateral wall contain a variety of ion pumps,
enzymes and transport proteins associated with
homeostatic mechanisms for maintaining the ionic
composition of the fluids of the cochlea.

In fact, the composition of the fluid within the scala media,
endolymph, is unusual for an extracellular fluid, containing
high potassium but low sodium levels at an unusually high
positive electrical potential (+ 80 m V) called the
endolymphatic potential (EP).

This contrasts with the scala tympani and scala vestibuli,
both of which are filled with perilymph that has high
sodium content and 0 m V electrical potential.

At the apex of the cochlea, these two outer chambers are
joined via an aperture called the helicotrema.


Maintenance of the EP is crucial to hearing.

As with both the stria vascularis and Reissner's membrane,
the cells of the organ of Corti facing the scala media are
joined by tight junctions.

Thus the whole of the scala media is chemically and
electrically isolated from the other scalae, the only
communication being through ion channels in the sensory
cells of the organ of Corti.

The EP is involved in driving currents through transduction
channels that are fundamental to hair-cell function and is
thus a vital component required for producing the high
sensitivity to the cochlea.

Cellular architecture and function of the
organ of Corti

The organ of Corti extends with a repetitively patterned
structure along the spiral for approximately 35 mm in
humans.

However, there are gradual variations longitudinally along
the cochlear spiral that systematically change the
mechanical characteristics of the organ of Corti-basilar
membrane complex.


The sensory region consists of two types of sensory hair
cell that are characterized by an apical bundle of hairs
called stereocilia.

In both cases, the stereo ciliary bundle projects into the
overlying endolymph from the apical flattened surface.

Inner hair cells usually form a single longitudinal row
running along the inner side of the sensory region with
respect to the centre of the spiral, whilst outer hair cells
form three rows running along the outer side of the
epithelium.

The number of outer hair cell rows may increase to four or
five over short, apparently random, lengths of the organ of
Corti, especially in basal regions of the cochlea.


There may also be additional inner hair cells outside the
normal single row.

These two types of hair cell are separated by two rows of
pillar cells forming a triangular arch-like structure in cross
section and enclosing the tunnel of Corti running lengthwise

The inner pillar row borders the inner hair cell row, and
the outer pillar row borders the innermost of the three
outer hair cell rows.


The hair cells have specific types of supporting cell
associated with each of them.

Inner phalangeal cells lying next to the pillar cells and
border cells lying next to the first inner sulcal cells
completely enclose the inner hair cells.

The outer hair cells are enclosed only at their bases and
their apices.

The base is held in the cup-shaped body of a Deiters' cell
which extends a thin phalangeal process up to contact the
apical part of adjacent outer hair cells.

The origin of the process is from the top of the cell body
and it projects at an angle towards the reticular lamina.


In the inner two rows of outer hair cells, the phalangeal
process passes alongside the neighbouring outer hair cell
to join the reticular lamina and form tight junctions between
the more apical outer hair cell in the row behind, and its
neighbour.

Thus, the Deiters' cell belonging to the base of one hair cell
supports the apices of the next two along the cochlea, but
in the row behind.

In the case of the third row of outer hair cells, the Deiters'
cells have the same basic pattern, but the process
terminates along the outer edge of the outermost row of
outer hair cells thus forming a border to the hair-cell region.

The arrangement of the Deiters cells and outer hair cells
produces a repetitive triangular structure underneath the
reticular lamina which is presumed to provide strong
mechanical support for the outer hair cells.


The apical regions of both supporting cells and hair cells
reach the upper surface of the organ of Corti.

But only in the supporting cells do the basal ends rest on the
basilar membrane, those of the hair cells held above the
basilar membrane within the supporting cell framework.

The upper surfaces of hair cells and their supporting cells,
and the pillar cells, are held together by tight junctions.

This system of junctions when viewed from above the organ
of Corti gives the appearance of a network in which the hair
cells and supporting cells are embedded, which has been
named the reticular lamina.

Beyond the third row of outer hair cells lie Hensen's cells
which contain large lipid droplets.

The outer edge of the organ of Corti curves down from the
reticular lamina, lined by the Hensen's cells, to a single layer
of cuboidal Claudius' cells which cover the remainder of the
basilar membrane out to the spiral prominence.


As well as the gradual narrowing of the basilar membrane,
the length of outer hair cells and their supporting cells
gradually decreases towards the basal end.

They also tend to be longer in the outermost row and shorter
in the innermost row, differences that are more pronounced
near the apex of the spiral and diminish towards the base.

The reticular lamina, which is oblique with respect to the
basilar membrane near the apex, becomes more parallel to it
near the base as the length of the outer hair cells decreases.

Other systematic changes include a gradual decrease in the
length and increase in the number of the stereocilia on both
hair cell types towards the base and other ultrastructural
features.

Hensen's cells become smaller and the tectorial membrane
changes in cross-sectional area, becoming thicker near the
basal end of the cochlea.


The functions of the organ of Corti are to detect sounds and
decompose them into their component frequencies, in the
process converting the physical vibrations into an electrical
response (mechanoelectrical transduction) and then
causing neural signals to be transmitted along the auditory
nerve and higher auditory pathway for central processing.

Sound pressure waves in cochlear fluids set up waves of
motion along the basilar membrane (called travelling
waves) which peak in different parts of the spiral according to
frequency, resulting in mapping of high to low frequency
components along its length.

The morphological gradients described above contribute to
this mapping by gradually varying the mechanical resonance
properties of the basilar membrane-organ of Corti complex.

The hair cells detect the basilar membrane motion, being
stimulated more strongly at the point coinciding with the peak
of the travelling wave than elsewhere.


The innervation pattern of the organ of Corti strongly
suggests that inner hair cells contribute most to the neural
signalling representing sensory transduction and
processing by the cochlea.

The cochlea is also known to contain an active amplifier
that enhances the ability to detect and separate frequencies
in sound.

The outer hair cells are thought to represent this amplifier,
mechanically boosting sound-induced vibrations of the
basilar membrane to produce a sharply tuned, highly
sensitive displacement pattern along the basilar membrane
that is reported by inner hair cells.

HAIR-CELL
ULTRASTRUCTURE AND
FUNCTION

Outer hair cells

The apical part of the outer hair cell is the sensory end, bearing
the stereociliary bundle, whilst the basal end consists of the
rounded synaptic pole where the cell connects with afferent and
efferent nerve fibres of the auditory nerve.

The apical surface is flattened and, when viewed from above,
triangular or heart-shaped whilst the cell bodies are cylindrical.

The stereocilia are arranged in a very pronounced W- or V-
shape.

The number of rows can be as much as five. The rows increase
in height across the bundle, like a staircase, along a radial axis
from the modiolus to the lateral wall.

In the case of the outer hair cells, the top of the bundle is in
contact with the underside of the tectorial membrane whilst the
inner hair stereocilia are probably free standing.


The stereocilia are cylindrical, narrowing sharply to an ankle
region where they join the cell and, at least in the intermediate
rows, with a bevelled tip.

They are angled towards each other so that they converge at
their tips. The shorter stereocilia are slightly narrower than the
intermediate and taller stereocilia.

Stereocilia contain a core of parallel actin filaments cross-
linked by the actin associated proteins plastin and espin.

In the lower third of the stereocilium, dense material becomes
associated with the centre of the core. Along with a group of
actin filaments, this extends down as a rootlet which contains
tropomyosin into an actin-rich filamentous mat, the cuticular
plate, located beneath the apical membrane.

The stereocilia also contain several unconventional (nonmuscle)
myosins and are enriched in calmodulin and other calcium
handling proteins.


The stereocilia are connected together by extracellular
filaments. A single filament, the tip link runs from the tip of
each stereocilium of the shorter rows to the side of the
adjacent stereocilium immediately behind.

At the upper attachment of the tip link, there is a distinctive
electron dense plaque lying between the membrane and
the actin core.

At the lower attachment there is dense material over the
actin core, separated by a gap from the membrane of the
tip.

Below the lower attachment is a zone called the contact
region where the membranes of the two converging
stereocilia approach very closely.

Lateral links connect the shafts of adjacent stereocilia, both
within and between rows. Where the lateral links connect to
the stereocilia, the membrane and the adjacent actin
filaments inside show an increased density.


The stereo ciliary membrane contains proteins associated
with calcium control (plasma-membrane calcium
ATPases) and mechanosensitivity (mechanoelectrical
transduction channels).

The transduction channels are associated with the regions
near the tips of the shorter stereocilia.

During transduction, they are gated (opened) mechanically
by movements of the hair bundle, which modulate their rate
of opening and closing.

Deflections of the bundle are driven by the motion of the
basilar membrane-organ of Corti complex that causes
shearing of the tectorial membrane parallel to the surface of
the organ of Corti.

This drives the outer hair cell stereociliary bundle
backwards and forwards.


Deflections in the direction of increasing stereociliary height
depolarize the outer hair cells by causing the channels to
open and allow an influx of cations, whilst opposing
deflections hyperpolarize the hair cells by closing the
channels.

The magnitude of the receptor potentials produced by
depolarizing deflections is increased by the high positive
EP (+ 80 m V) which, together with the resting membrane
potential of the hair cell (around -70 mV), results in a
much greater potential difference than normally present
even in neurones of 150 m V between endolymph and the
inside of the hair cell.

This large driving force increases the sensitivity of the
sensory cells substantially.

The tip link represents a 'gating spring' for the transduction
channels, a physical mechanism to open them.


The hair bundle may also have an active role in
mechanical amplification. The bundles show evidence of
force production that produces active motion which
adjusts the position of the bundle (adaptation).

The rapid force production driven by a calcium-dependent
process could enhance the mechanoelectrical transduction
response to amplify the very smallest stimuli.

Again, the high EP would make this amplification more
effective.

The unconventional myosins could interact with actin in the
stereocilia providing one source of such force production.

The cuticular plate contains actin filaments that are more
randomly organized into a meshwork than the parallel
bundle found in the stereocilium. Nevertheless, there are
regional differences and structural features in the cuticular
plate that indicate a high level of organization in both the


The cuticular plate is interrupted in the region just behind
the stereociliary bundle and adjacent to its centre. Here, a
channel of cytoplasm runs through the plate to the apical
membrane. This channel contains a basal body.

The cuticular plate acts as an anchoring structure for the
stereocilia but could also be a site where the mechanical
properties of the hair bundle are modified via the rootlets.


In the cell body, there is a concentration of Golgi apparatus,
mitochondria and endoplasmic reticulum just beneath the
cuticular plate and many outer hair cells contain a large
body (Hensen's body) composed of multiple concentric
layers of membrane, especially in cells near the cochlear
apex.

These layers appear to be contiguous with a stack of
submembraneous cisternae lying just beneath the plasma
membrane and extending down the side from near the
cuticular plate to the level of the nucleus.

The nucleus is spherical and situated in the basal region of
the cell.

The plasma membrane contains a protein called prestin
that changes shape when subjected to a voltage change.

Isolated outer hair cells can be made to undergo very fast
contraction-elongation cycles by electrical stimulation, a
property called electromotility.


Isolated outer hair cells can be made to undergo very fast
contraction-elongation cycles by electrical stimulation, a
property called electromotility.

The cortical lattice is believed to act as a cytoskeletal spring
involved in converting the voltage-evoked conformational
changes in prestin into the movement of the whole hair cell.

This outer hair cell motility is generally regarded as the
main source of active cochlear amplification

An alternative or additional source of amplification may be
the hair bundle.

Synaptic specializations associated with afferent and
efferent terminals are present in the basal pole.


The outer hair cells show other gradients in ultrastructural
morphology along the length of the cochlear spiral and also
across the three rows.

These gradients are presumed to reflect differences in cell
physiology and micro mechanics that contribute to the
systematic changes in properties of the organ of Corti-
basilar membrane complex.

Inner hair cells

The inner hair cells have a flattened or slightly concave
apical surface that is ovoid when viewed from the scala
media and a flask-shaped cell body with a wide centre
tapering basally and apically.

The inner hair cell stereo ciliary bundle consists of three to
four relatively linear rows of stereocilia, their long axes
running parallel with the hair-cell row.

However, there is often evidence of a shallow notch
approximately halfway along where the rows indent slightly,
and the ends of the bundle tend to curve round to some
degree towards the modiolus.

The effect of these features is to produce a shallow version
of the more pronounced W-shape of outer hair cells,
although the stereo ciliary arrangement is less precise.


Each row contains stereocilia of generally similar height,
though tending to shorten near the ends of the row.

The height of the rows increases in a step-wise manner
across the bundle from the modiolar to the strial side.

The stereocilia themselves are cylindrical actin-containing
structures, with bevelled tips in the second tallest row and
rounded tips in the others, and narrow ankles.

The stereocilia have dense rootlets that penetrate into an
apical cuticular plate and thus appear to be anchored
within.


Externally, the stereocilia are again connected together by
filamentous lateral links, which bind them both sideways
and across the rows, and a contact region and tip links.

The process of transduction by hair cells is similar to that
described for outer hair cells.

However, unlike the tallest stereocilia of the outer hair cells,
the inner hair cell stereocilia do not appear to insert into the
tectorial membrane.

Thus, sound-induced motion of the basilar membrane is
thought to stimulate the inner hair cell bundle via fluid
motion of the endolymph between the tectorial
membrane and the hair cell apex.


The cell body contains a region rich in Golgi bodies,
endoplasmic reticulum, mitochondria and other evidence of
synthetic activity just below the cuticular plate and the neck of
the hair cell.

The centre of the cell is occupied by a large spherical
nucleus, with clusters of mitochondria and endoplasmic
reticulum around it.

Beneath the lateral plasma membrane in the neck region and
extending down to the level of the nucleus is a single layer of
cisternal membranes.

The space between these membranes and the plasma
membrane contains a cortical lattice of actin and spectrin
filaments and rows of pillars connecting to the membrane
similar to that of outer hair cells.

However, there is no evidence of prestin in the membrane of
the inner hair cells, and they do not appear to display electro
motility like that of outer hair cells.


The basal end of the cell is the synaptic pole where the
terminals of the afferent auditory nerve fibres make
synaptic contact.

This region is filled with vesicles and coated and uncoated
membraneous tubules and has synaptic specializations
called synaptic ribbons with associated synaptic vesicles.

Depolarization of the hair cell is believed to result in
calcium-dependent vesicular release of the amino acid
glutamate onto the postsynaptic afferent terminal, which
contains glutamate receptors.

This depolarizes the nerve ending, resulting in the
generation of action potentials.

Efferent contacts directly onto inner hair cells are rare.

ULTRASTRUCTURE OF
SUPPORTING CELLS


Deiters' cells are associated with outer hair cells, and are
also called outer phalangeal cells. The latter name arises
from the presence of the phalangeal process that extends
up from the body of the Deiters' cell.

The process is supported by one or more microtubular
bundles that appear to originate in basal filamentous
material and end in the apical junctional complex and
associated material.

The Deiters' cell cup contains dense material directly
beneath the outer hair cell base which is rich in actin and
appears to be physically strongly attached to the hair-cell
base.


The inner phalangeal and border cell lateral membranes
are closely associated with that of the inner hair cell on the
strial and modiolar sides respectively.

Both cells are longer than the hair cell and jointly surround
the basal pole before extending down to attach to the
basilar membrane next to each other where their nuclei are
located.

At their tops, they are connected to the hair cell and other
supporting cells by junctional complexes.

Both cells display finger-like projections that interdigitate
with afferent auditory nerve fibres as they approach the
base of the inner hair cell.

These cells are presumed to have a protective role
because they strongly express transporters associated with
glia-like uptake of glutamate after its release from the hair
cells.


Between the two hair cell types are the two rows of inner
and outer pillar cells, or rods of Corti.

These cells are supported by a thick microtubular bundle
emanating from apical and basal filamentous zones
composed of actin and other cytoskeletal proteins.

The two pillar cells have radial feet resting on the basilar
membrane above which the pillars are angled towards each
other, forming the arch over the tunnel of Corti, the rounded
head of the outer pillar cell contacting the concave
underside of the head of the inner pillar cell in a strong joint
held together by junctional complexes.

Thus, the inner pillar cell head curves over the top of the
outer pillar cell head and forms a rectangular profile
obscuring the top of the outer pillar cell when viewed from
above the reticular lamina, and lying between the inner hair
cells and first row of outer hair cells.


The outer pillar, however, produces a process from the side
of the head region, which contains a microtubular bundle,
and extends up to the reticular lamina in the direction of the
stria vascularis.

It surfaces between two adjacent outer hair cells of the first
row.

Like all other supporting cells in the organ of Corti, the outer
pillar cell has an apical surface exposed to the endolymph.

The cytoskeletal organization of pillar cells strongly
suggests that they have an important role in providing
physical support to the organ of Corti.

INNERVATION OF THE ORGAN OF CORTI


Acoustic information from the hair cells is transferred by the
auditory portion of the VIIIth cranial nerve (the
vestibulocochlear nerve) to the ipsilateral cochlear nuclear
complex in the brain stem.

The auditory nerve is composed of afferent fibres projecting
from spiral ganglion neurones, the cell bodies of which
reside in the modiolus, just central to the osseus spiral
lamina.

The spiral ganglion thus follows the course of the organ of
Corti inside the modiolus.

The neurones are of two types, type I that innervate the
inner hair cells and type II that innervate the outer hair cells.

The afferent innervation of the two hair cells types differs
considerably in both number and distribution of fibres.


The majority of spiral ganglion neurones (up to 95 percent)
are type I and innervate the inner hair cells in a convergent
manner.

Up to 20 type I neurones innervate each inner hair cell
via a peripheral process that terminates on the hair-cell
base at a ribbon synapse.

These synapses consist of post-synaptic density on the
afferent terminal and a presynaptic density on the hair cell
membrane, attached to which is a dense presynaptic ribbon
or bar.

A single layer of synaptic vesicles usually clusters around
the bar.


The cell body of the type I spiral ganglion neurone, its
peripheral process and the central axon, which projects to the
cochlear nucleus, are myelinated.

The peripheral process becomes unmyelinated in the osseus
spiral lamina just before it enters the organ of Corti through a
hole (the foramen nervosum) in the upper border of the
spiral lamina, the habenula perforata, to approach the inner
hair cell.

At the hair-cell base, each process widens into a bulb where
the synapse forms. The central process enters the modiolus.
At the apex of the cochlear spiral, the central processes enter
the middle of the modiolus and, progressively down the spiral,
more are added successively to the periphery of the nerve.

Thus, as the nerve grows to its maximum diameter where it
exits through the internal auditory meatus at the base of the
spiral, low frequency fibres occupy the centre of the auditory
nerve, with fibres of increasingly higher frequency found
towards the periphery.


The responses of the type I auditory nerve fibres reflect the
input from inner hair cells.

When the inner hair cell is depolarized it releases a
neurotransmitter, generally believed to be glutamate, from
the presynaptic vesicles onto post-synaptic glutamate
receptors on the nerve ending which itself then becomes
depolarized.

Provided the amount of depolarization is sufficient, this
triggers action potentials in the nerve fibre.


As noted above, a fibre originating near the base of the
cochlea will have its best response to a high frequency, and
one originating near the apex to a low frequency.

For any tone, the peak of the travelling wave will occur at
the point of maximum resonance on the spiral for that
frequency.

If the tone is loud enough after cochlear amplification,
there will be sufficient displacement of the inner hair cell
stereocilia to depolarize the hair cell and evoke action
potentials in the attached cochlear nerve fibre.

The number of action potentials per second increases with
increasing sound intensity and for frequencies below 5
kHz, the action potentials can become phase locked (i.e.
occur at a particular point in the cycle) and so provide
information on the frequency content of the stimulus as well
as the intensity.


Each individual nerve fibre is thus defined by its characteristic
frequency, which is the frequency for which it has its lowest
threshold.

For each fibre, the threshold increases (i.e. there is a weaker
response) for tones that are higher or lower than the
characteristic frequency, reflecting the change in position of the
peak of the travelling wave and the narrowness of the peak. The
latter depends on the cochlear amplifier.

Thus, the sharpness of tuning of the basilar membrane organ of
Corti complex is represented by the sharpness of tuning of the
inner hair cell and the nerve fibre.

This, in turn, ultimately determines the ability of the auditory
system, to distinguish between sounds of different frequency.

When the amplifier is impaired, for example through loss of
outer hair cells, fibres will have higher thresholds and broader
tuning, making separation of frequencies (frequency selectivity)
poorer and requiring louder sounds to evoke a response.


The type II neurones innervate the outer hair cells in a
divergent manner and tend to be smaller than the type I
neurones. Their peripheral processes and central axons are
unmyelinated.

The peripheral processes enter the organ of Corti through
the same route as that of the type I processes, and traverse
the inner hair cell and inner pillar cell rows, crossing the
floor of the tunnel of Corti as basilar fibres.

They then travel towards the cochlear base for varying
distances as outer spiral fibres, before branching to
innervate up to ten outer hair cells each.

The relatively small number of fibres to the outer hair cells,
which are three times more numerous than inner hair cells,
suggests they are not the primary signalling pathway
from the cochlea, and indeed type II cells are difficult to
record from using microelectrodes, unlike the type I cells.


Tthe auditory nerve alos contains myelinated and
unmyelinated efferents that represent descending
projections from the brainstem.

The majority of the myelinated fibres end on outer hair cells
directly, whereas the majority of unmyelinated efferent
fibres end on the peripheral processes of afferent auditory
nerves just below the inner hair cell.

SUMMARY OF FUNCTIONAL
PROPERTIES OF THE ORGAN OF CORTI-
BASILAR MEMBRANE COMPLEX


The cochlea performs frequency analysis, splitting complex
sounds up into component tones and signalling that
information to the brain. Thus the cochlea responds to
sound stimuli by:
− producing travelling waves along the basilar
membrane that peak more apically for decreasing
sound frequency and whose amplitude reflects
the intensity of the sound;
− detecting the motion of the basilar membrane
through deflection of the stereocilia which
produce receptor potentials in the hair cells
graded in size with the amplitude of the motion.

− enhancing the motion of the basilar membrane
with a biomechanical amplifier residing in the
stereo ciliary bundles and/or the outer hair cell
lateral wall (somatic motility); enhancement is
nonlinear and maximally amplifies motion at the
point of maximum response, hence producing
high frequency selective peaks in the travelling
waves;
− detecting the resultant basilar membrane motion
through deflection of inner hair cell stereocilia
which results in neurotransmitter release and the
production of action potentials in the auditory
nerve fibres.

− The frequency is encoded by
• (1) the place of origin of the nerve fibres (i.e.
those connected to the hair cells which are
being stimulated most) and
• (2) the timing of action potentials (for
frequencies below 5 kHz), whilst intensity is
coded by the rate of action potential firing.


The main evidence for the duplex activity of the hair cells in
the cochlea is:
− the differential distribution of innervation with
afferent fibres mainly to inner hair cells and
efferent fibres mainly to outer hair cells, indicating
inner hair cells are the main signalling pathway;
− selective loss of outer hair cells produced by
amino glycoside antibiotics which causes a
reduction in sensitivity and frequency selectivity
(broadening of tuning), indicating their primary
role in determining these properties compared
with inner hair cells;
− otoacoustic emissions (sound generated within
the cochlea) which is evidence of active
amplification;

− evoked motility of the outer hair cells in vitro and
in vivo, the latter also capable of generating
otoacoustic emissions which suggests they are
the site of an active process;
− active force production by the outer hair cell
stereocilia that has been observed in the adult
mammalian cochlea in vitro.

THE ASCENDING
AUDITORY PATHWAY


The output of the cochlea travels along auditory nerve fibres a short distance in the
cochlear nerve before entering the brainstem. There are several regions that participate
in the afferent auditory pathway between the cochlear nerve and auditory cortex. In
ascending order, the most important of these are the cochlear nuclear complex, superiory
olivary complex, inferior colliculus, medial geniculate nucleus and then auditory cortex
(Figure 226.10).

The pattern of connections between these nuclei is complex and not fully understood, and
only the main nuclei and projections are represented in Figure 226.10. As can be seen,
there are commissural connections at various points and multiple collaterals that make
the pathway very intricate. What follows is a simplified description that covers the main
stages of the auditory pathway and their likely functions.

The cochlear nuclear com plex

The cochlear nuclear complex is subdivided into dorsal cochlear nucleus (DCN) and
ventral cochlear nuclei, the latter composed of anteroventral cochlear nuclei (AVCN) and
posteroventral cochlear nuclei (PVCN).20 These three regions are distinguishable on the
basis of their location and cytoarchitecture (the range of cells of different morphology).
The central processes of type I spiral ganglion neurones enter the cochlear nuclear
complex and immediately bifurcate, sending branches to the DCN or PVCN and the
AVCN. Low frequency fibres divide ventrally, and high frequency fibres dorsally so that
the cochleotopic map of frequency, represented anatomically by the distribution of fibres
in the auditory nerve, is maintained across the cochlear nuclei as a tonotopic map of
neurones responding to progressively higher frequency from one side to the other.

The auditory nerve afferents in the AVCN terminate on the principal projection neurones
of the cochlear nuclear complex, the spherical/bushy cells, so called because they have
round cell bodies and bushy dendritic fields (Figure 226. 1 1a-d). The end of most
auditory nerve fibres expands into a single very large terminal, the end bulb of Held,
which cups around the soma of the spherical cell (Figure 226. 1 1c) (very low frequency
neurones, <1 kHz, may branch to form two endbulbs). One or two such terminals are
found on each spherical cell. This large excitatory terminal contains large numbers of
round neurotransmitter vesicles typical of glutamatergic terminals (Figure 226. 1 1e) and
ensures rapid transmission of the signal from the auditory nerve fibre that faithfully
preserves the original frequency selectivity and sensitivity of the cochlear response.
Accordingly, these cells have electro physiological responses to sound that are called
primary-like because they reflect the primary input from Auditry nerve fibres. However, in
the DCN or PVCN, several auditory nerve fibres may contact a single multipolar (or
stellate) cell, which have more complex responses. This multiple input means these cells


Also in the PVCN are octopus cells, which have an extended dendritic field lying across a
number of auditory nerve fibres, so that they receive input representing a range of
frequencies. These cells respond rapidly and may be responsible for determining the
precise time of arrival of sounds. They also send signals to motor nuclei in the brain stem
and midbrain so they may be involved in acoustic startle responses, where loud or
unexpected sounds evoke movement.

As well as these projection neurones, the cochlear nuclei contain interneurones and
receive inputs from higher up the auditory pathway that produces inhibition and generates
more complex responses in some neurones. In particular, it has been suggested that
these complex responses in the DCN are important in determining what sounds are.

The superior olivary com plex

The auditory pathway splits as it leaves the cochlear nuclear complex. The dorsal
pathway projects directly to the inferior colliculus, the ventral pathway divides further and
projects to both the ipsilateral and contralateral superior olivary complex (Figure 226.10).
This makes the superior olivary complex the first part of the ascending auditory pathway
where major binaural comparisons can be made.

The superior olives receive binaural information from spherical/bushy cells. This arises
from collaterals from the output fibres of the cochlear nuclei on the same side that then
cross over to the opposite superior olivary complex. This enables the superior olives to
function in sound localization. Each superior olivary complex contains an Sshaped lateral
olivary nucleus, a disc-shaped medial olivary nucleus (Figure 226. 10) and the medial
nucleus of the trapezoid body together with smaller periolivary nuclei. Within the medial
olivary nucleus, there are neurones that use the binaural inputs to compare the time of
arrival of sounds to each ear. For example, for a sound coming from the left of a person's
head, the left ear would receive the sound first, the right ear second because of the
difference in distance to the two ears. The further to the left, the greater the difference in
time of arrival. From experimental work in owls, computation of the interaural time delay
would allow the medial olivary nucleus to localize a sound.21 In fact, a spatial map seems
to be present, represented by gradual changes in the responses of the neurones across
the anterior-posterior axis of the medial olive to specific interaural time differences. This
method of localization would work for discontinuous sounds and for relatively low
frequency continuous tones, but breaks down at higher frequencies for continuous tones
because individual auditory nerve fibre responses cannot encode accurate timing
information above 5 kHz due to limitations on the rate of firing of action potentials.


Sound localization at higher frequencies may be carried out by comparing sound
intensities.22 If a sound source is on the left of a person's head, as before, it is closer to
the left ear than to the right and so sounds louder. Neurones that detect differences in
sound intensity are located in the lateral superior olives. Most of these neurones receive
an excitatory input from the ipsilateral cochlear nucleus and an inhibitory one from the
contralateral cochlear nucleus. Thus if a sound is of equal intensity in both ears because
it originates on the midline, the inhibition and excitation of the binaural neurones between
the two nuclei balances out. If, however, a sound is louder in the left ear, the excitation
will be stronger for the neurones in the ipsilateral olive and the inhibition weaker
enhancing the ipsilateral response, whilst the converse will hold true for the neurones in
the contralateral olive, which will have a much weaker response.

Inferior col liculus

There are four bumps on the surface of the midbrain, which together form the corpora
quadrigemina. These are composed of the two superior and two inferior colliculi. The
inferior colliculi receive direct input from the brainstem auditory nuclei via a tract called
the lateral lemniscus. Each of the inferior colliculi consists of a central nucleus which
receives the major auditory input, and an outer region composed of a dorsal cortex and
an external lateral cortex. The external portions of the inferior colliculus receive
connections from cerebral cortex and from mutimodal sources respectively.

In the inferior colliculi, the two pathways that emerge from the cochlear nuclear complex
join together again for further analysis. More complex responses are found in inferior
collicular neurones, and further features are extracted and mapped towards
understanding 'what a sound is'. The central nucleus is layered into isofrequency bands
(Figure 226. 1 2a). Along each band, the cells have flattened dendritic fields and respond
best to approximately the same frequency. The higher frequency bands are found
towards the midline of the brain, low frequency bands more towards the outside,
producing a tonotopic map. Superimposed on each band is another map that relates to
intensity. This is best visualized by thinking of each isofrequency band as a disc. The
cells in the centre of the disc have low thresholds which means they respond to quiet
sounds, whilst moving out to the periphery of the disk there are concentric areas in which
the threshold of the neurones increases, hence requiring louder and louder sounds to
stimulate them (Figure 226. 12b). There are also neurones that respond to timevarying
stimuli,22 such as changes in frequency (frequency modulated - for example, a sound
moving towards you or away, such as an aeroplane) or in intensity (amplitude modulated
- for example, an air-raid siren) . These responses also seem to be mapped
approximately from front to back across each inferior colliculus.


These intersecting maps in the inferior colliculi are thus able to extract complex features
of sounds. At the next nucleus in the auditory pathway, cells have been found that
respond to particular complex sounds, for example, the mew of a kitten. These maps in
the inferior colliculus thus provide a basis for recognizing patterns in sound. There are
also neurones in the inferior colliculus that are involved in sound localization; as many as
threequarters of the neurones may have binaural responses. These neurones may
provide input to the superior colliculus in which there are visual and auditory space maps
that can therefore be compared so that sounds can be assigned to specific objects.

The inferior colliculus is also involved in auditorymotor responses, for example, controlling
middle ear muscles, which can be used to attenuate loud sounds and protect the ear. In
addition, there are projections to motor nuclei that contribute to turning the head or
moving the eyes in response to sound.

The m ed i a l g e n i c u l ate n u clei and a
u d itory co rtex

The thalamus contains three regions where auditory influence is known to occur, the
medial geniculate body, the posterior nucleus and part of the reticular nucleus of the
thalamus. The most important for auditory function are the geniculate nuclei which are
bilateral rounded regions lying on the surface of the thalamus. These nuclei have three
major divisions each receiving a separate, parallel pathway from the inferior colliculus.
The ventral division is organized to no topically into isofrequency layers within which there
are ordered maps of neurones responding to different auditory cues and is the tonotopic
pathway, receiving its input from the central nucleus of the inferior colliculus. Secondly,
the diffuse pathway enters the dorsal division and is not tonotopically organized, arising
from the dorsal cortex of the inferior colliculus. The cells here respond to many different
frequencies, many only to complex sOUIlds.23 The medial division receives multimodal
inputs from external lateral cortex of the inferior colliculus involving several other sensory
systems including the auditory system. Neurones within this division thus respond to one
or more modality and can be modified by learning.


The main projection to the primary auditory cortex arises from the ventral division of the
medial geniculate nucleus and terminates in area Al, corresponding to Brodmann's area
4l in the human brain, within the lateral fissure of the temporal lobe (Figure 226.13a). The
dorsal division of the medial geniculate nucleus projects to the non-primary auditory areas
around Al, and the medial division projects diffusely to the whole region and to
surrounding cortical fields.

Al, like the preceding auditory nuclei, is organized into isofrequency layers arranged
tonotopically from low frequency in the rostral end to high frequency in the caudal end
(Figure 226.1 3b),z4 Most cells within Al respond t o binaural stimulation. There are two
main types of response: neurones that summate excitatory responses from both ears and
neurones that receive excitatory stimulation from one ear and inhibitory stimulation from
the other. Bands of cells displaying excitation-excitation and excitation-inhibition
responses run alternately across the isofrequency layers (Figure 226. 1 3c) . The main
function of these cells, and of primary auditory cortex in general, appears to be sound
localization.

Complex responses can be found in neurones in the areas surrounding Al. These include
responses to features such as specific delays between significant parts of a complex
sound, and the simultaneous occurrence of harmonically related frequencies. These
types of feature extraction are likely to be important in the analysis of time-varying
acoustical signals such as human speech.23


There are descending projections from each of the stations of the ascending auditory
pathway, down as far as the cochlear nuclei and from the superior olivary complex to the
cochlea. Some of these descending projections may participate in attention level and
anticipation of signals.

The olivo cochlear feedback loop is a major descending projection. Following afferent
input to the superior olives, fibres completing this loop originate from neurones in or
around the superior olivary complex and project back along the auditory nerve into the
cochlea. Those originating adjacent to the contralateral medial superior olives, which
cross the midline and are myelinated, form the majority and constitute the crossed
olivocochlear bundle. They contribute largely to the efferent projection to the outer hair
cells (Figure 226.9c), also known as the medial efferent system. The fibres end in
relatively large primarily cholinergic nerve terminals next to a subsynaptic cistern in the
hair cells, and contain large numbers of vesicles (Figure 226.ge ) . It is believed they
function to suppress outer hair cell motility to make the cells less sensitive, providing
protection from very loud sounds.

A smaller number of unmyelinated efferents originate from the lateral superior olive
ipsilaterally and contribute mainly to the efferent projection synapsing with the peripheral
processes of type I spiral ganglion neurones beneath the inner hair cells (Figure 226.9f),
although a few terminate directly on the hair cells. This has been called the lateral
efferent system and may comprise two functional subdivisions, capable of inducing either
slow increases or decreases in the magnitude of the response of auditory nerve fibres.
Since these fibres originate in the lateral superior olive, which is involved in sound
localization, they may be useful in maintaining accurate binaural comparisons during slow
changes in interaural sensitivity.25

Cochlea

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