Auditory System Part 1

The Behavioral Relevance of Sound

As shown below, sound plays a variety of important roles in the lives of all animals, including humans.

What Is Sound?

Sound is produced when something vibrates →The vibration disturbs the air around it.
This creates periodic changes in air pressure.
• Rarefaction (low pressure)
• Condensation (high pressure)
These changes in air pressure move through the air as sound waves.

Components of a Sound Wave

1. Wavelength (meters/cycle) is the horizontal length of one cycle of the wave.

2. Period (seconds) is the time required for one complete cycle of the wave to
pass a fixed point.
3. Amplitude (decibels) is the height of the wave and is correlated with the
loudness of a sound.
4. Frequency (hertz) is the number of cycles per second that pass a fixed point.

Frequency (f) and period (t) are related:

• f = 1/t
• t = 1/f
Sounds classified by frequency (based on human frequency sensitivity):
• Infrasound: < 20 Hz
• Audible Range: 20 Hz – 20,000 Hz
• Ultrasound: > 20,000 Hz

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 Measuring Sound Amplitude (Intensity)

Derived parameter for measuring sound amplitude is sound pressure level (SPL).

The human ear is incredibly sensitive - In terms of power, the sound of a jet engine is
about 1,000,000,000,000 times more powerful than the smallest audible sound.

As a result, The decibel (dB) is the unit used to measure the intensity of a sound.

On the decibel scale, the smallest audible sound (near total silence) is 0 dB. A sound
10 times more powerful is 10 dB. A sound 100 times more powerful than near total
silence is 20 dB. A sound 1,000 times more powerful than near total silence is 30 dB.

Most natural sounds are complex, consisting of two or more frequencies in

combination.

Both the amplitude and frequency of a sound can vary with time.
1. Amplitude Modulation (AM)
2. Frequency Modulation (FM)
Sound Features Used for Sound Recognition

Frequency (spectral) content (frequency domain) and pattern of amplitude modulation

(time domain) uniquely identify different sounds.

Both the time and frequency information contained within a sound are extracted by the
auditory system and used for sound recognition.

This is illustrated below:

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Oscillographic (top) and sonographic (bottom) analysis of two different spoken phrases showing their unique
spectral and temporal features.

The intensity of a particular frequency component is represented on a gray scale. The darker the shading, the more
energy there is at that frequency.
How is Time and Frequency Information Extracted by the Nervous System?

The human ear, like that of most vertebrates, is a pressure receiver.

There are 3 distinct regions of the ear:
1. Outer ear
2. Middle ear
3. Inner ear
Outer Ear
The outer ear is comprised of the following:
1. Pinna
2. Concha
3. Meatus
4. Tympanic Membrane

Pinna funnels sound pressure waves into the meatus where they induce
movement of the tympanic membrane.

The outer ear amplifies frequencies in the range of 2 kHz – 6 kHz; these are critical spectral components of speech.
Middle Ear
The middle ear is comprised of the following structures:
1. Malleus
2. Incus
3. Stapes
The three bones of the middle ear also called the ossicles.

Couple outer ear to inner ear.

Functions as an impedance matching device for the efficient transfer of acoustic energy from compression waves
in air (low impedance) to fluid–membrane waves (high impedance) within the cochlea.

Inner Ear

The inner ear comprises the following:

1. Vestibular System (balance)
2. Cochlea (hearing)

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 The Cochlea

Cochlea coiled like snail shell.

Three fluid-filled chambers:
1. Scala Vestibuli (fluid is called perilymph; High K+, Low Na+ Concentration)
2. Scala Tympani (fluid is called perilymph; High K+, Low Na+ Concentration)
3. Scala Media or Cochlear Duct (fluid is called endolymph; Low K+, High Na+ Concentration)

Cochlea contains the auditory end organ, the Organ of Corti, responsible for mechanoelectrical transduction.

The Organ of Corti

The Organ of Corti is comprised of:

1. Tectorial Membrane
2. Basilar membrane
3. Inner Hair Cells – 1 row
4. Outer Hair Cells – 3 rows

The Organ of Corti extends along the entire length of the Cochlea.

Hair Cells [left is inner and right is outer]

• Inner hair cells are globular

• Outer hair cells are cylindrical

• Both are coupled to the basilar membrane

• Inner hair cells have 3 rows of stereocilia that

are graded in height.
• Outer hair cells have 3 rows of stereocilia that are organized in a W-shape and graded in height.

• Stereocilia of outer row of outer hair cells are embedded in the tectorial membrane.
• Stereocilia of the remaining two rows of outer hair cells and those of the inner hair cells are loosely attached to
the underside of the tectorial membrane.

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Inner hair cells transform the sound vibrations in the fluids of the cochlea into electrical signals that are then relayed
via the auditory nerve (cranial nerve VIII) to the auditory brainstem.
Outer hair cells do not send neural signals to the brain, but mechanically tune and amplify low-level sounds that
enters the cochlea.
The role of the cochlea in the process of auditory transduction is described in the video below.

AUDITORY SYSTEM PART 2

Mechanoelectrical Transduction

The transduction of an auditory signal into a neural signal is referred to as mechanoelectrical transduction.

As you will see, this is due the energy involved in the mechanical displacement of the basilar membrane into a
receptor potential at the level of the inner hair cell.

Transduction takes place within the Organ of Corti, a confocal microscope image of which
is shown at left. Hair cells have been labeled with a green fluorescent stain. The single
row of inner hair cells can be seen inf front, with the three rows of outer hair cells in back.

General Features of Mechanoelectrical Transduction

In the model proposed at left, a transduction channel is anchored by intracellular and

extracellular anchors to the cytoskeleton and to an extracellular structure to which forces
are applied.

The transduction channel responds to tension in the system, which is increased by net
displacements between intracellular and extracellular structures.

Does such an arrangement exist at the level of the hair cell? The answer of
course is, yes!

In the EM photomicrograph above you can see the protein-based tip links connecting the stereocilia of an inner hair
cell. These are the "extracellular links" proposed in the model presented above.

Shown below left, is more biologically realistic molecular model for hair cell transduction.

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 When tension on the tip link increases (bending of the stereocilia towards the tallest row),
transduction channels open and the cell depolarizes.

When tension on the tip link decreases (bending of the stereocilia towards the shortest row), transduction channels
close and the cell hyperpolarizes.

What causes the bending of the tip links?

The relative motion of the basilar membrane and tectorial membrane resulting from fluid displacement in the
cochlea exerts a shearing force on the stereocilia triggering a transduction event.

Ionic Basis of Mechanoelectrical Transduction

The sequence of events is shown in the figure below:

To summarize:

• The apical end of the inner hair cells is bathed in endolymph (high
K+).
• The basal end of the hair cells is bathed in perilymph (low K+).

1. Deflection of stereocilia towards the tallest row increases

tension on tip links.
2. Transduction (stretch-activated) channels open.
3. K+ flows into the cell depolarizing it. The ionic current
designated, Ik
4. Voltage-gated Ca+2 channels open.
5. Ca+2 flows into the cell depolarizing it further. This also
triggers neurotransmitter release from basal end of hair
cell. The ionic current designated, ICa
6. Increased [Ca+2]I opens K+ channels at basal end of hair cell.
7. K+ flows out of the cell, repolarizing it. The ionic current designated, IKCa
8. Ca+2-ATPase pumps Ca+2 out of cell restoring its balance.

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 Information Processing - Frequency Coding

How is the frequency information embedded in the Wren’s song, and that of other sounds for that matter,
extracted and coded by the vertebrate ear?

There are 3 different mechanisms, 1 passive and 2 active.

Frequency Coding - Passive Mechanism

The passive mechanism involves the micromechanics of the basilar membrane.

As shown below, the width of the basilar membrane changes with length - it is narrow at base; wide at apex.

• Because of change in width, the stiffness

(compliance) also changes with length - it is stiff
at the base; flexible at apex.
• The dispersion of fluid waves in the scala vestibuli
and scala tympani causes sound input of a certain
frequency to vibrate some locations of the
membrane more than other locations.

As shown in experiments by Nobel Prize laureate Georg

von Békésy, high frequencies lead to maximum vibrations
at the basal end of the cochlear coil, where the membrane is narrow and stiff, and low
frequencies lead to maximum vibrations at the apical end of the cochlear coil, where the
membrane is wider and more compliant.

As a result, the basilar membrane exhibits tonotopic organization (left) where sound
frequency is represented systematically along its length as shown below.

What does this mean?

• As shown at left only those inner hair cells sitting directly above the displaced
regions of the basilar membrane would be maximally excited.
• Moreover, the degree of excitation is dependent upon the amplitude of a particular frequency at a particular
time; greater amplitude, greater displacement of the basilar membrane, greater the depolarization of the hair
cell.
• Thus, within the inner ear, there is a PLACE CODE for frequency, as excitation
of inner hair cells is dependent upon their position along the cochlear partition.
• Complex sounds result in the differential activation of numerous inner hair cells
depending upon the distribution of spectral energy.

The pattern of inner hair cell excitation provides information about the spectral content of
a sound representing an across-fiber coding scheme for the frequency content of a complex
sound.
This is illustrated below:

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 Frequency Coding – Active Mechanisms

Electrical Resonance
During sustained depolarization, the membrane potential of inner hair cells resonates at a specific frequency.

• Above, patch clamp records are shown immediately below the hair
cells, while change in receptor potential is shown immediately below
the patch clamp records.
• Note the damped oscillation in membrane potential as the hair cell
depolarizes, repolarizes, then depolarizes again etc. due to the
continued depolarization of the hair cell - this continues until the
depolarization of the hair cell ends.
• This is due to relative kinetics of IKCa and ICa activation and
inactivation.
• When stimulated acoustically, hair cell output is greatest when the
stimulus frequency matches the resonant frequency of the hair cell.
• Thus, hair cells are “electrically tuned”.
• Electrical resonance is particularly effective at frequencies < 500 Hz.

Electromotility

• Outer, but not inner, hair cells express the contractile protein, prestin (immunohistochemically labeled
below), which is localized to their outer membrane.
• When outer hair cells are depolarized, prestin undergoes a conformational change
resulting in hair cell contraction
• Because of coupling to tectorial and basilar membranes, contraction alters
micromechanics of cochlea.
• Result is to amplify and tune basilar membrane displacement, thereby enhancing signal
detection and frequency selectivity.
• The effect on the amplitude of basilar membrane vibration with and
without the contractile mechanism is shown at left.
• Obviously, hair cells over the region of displacement would
depolarize much greater in response to a specific frequency with the
contractile mechanism than without.

The Vestibularcochlear (8th) Nerve

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Each inner hair cell is innervated by 10 – 15 bipolar cell fibers originating in the spiral ganglion as shown below.

Afferents arising from bipolar neurons in the spiral ganglion (above) form the vestibulocochlear nerve.

As shown below, axons of spiral ganglion cells join those coming from the vestibule to form the vestibulocochlear
nerve (8th cranial nerve)

Fibers in the VIIIth nerve transmit encoded auditory information into the CNS at the
level of the medulla oblongata in the brainstem.

Auditory System Part 3

Axons of spiral ganglion cells join those coming from the vestibule to form the
vestibulocochlear nerve (8th cranial nerve) which transmits encoded auditory
information into the CNS .

How is auditory information encoded at the level of the 8th nerve?

Frequency Coding

• The frequency sensitivity of 8th nerve fibers is defined by the inner hair cells that they innervate.
o Remember, 8th nerve fibers are the axons of spiral ganglion cells that innervate hair cells.
• The frequency selectivity of 8th nerve fibers is described by their excitatory frequency tuning curves.
• Excitatory frequency tuning curves represent the “excitatory receptive fields” of 8th nerve fibers.

• How are frequency tuning curves generated?

o As shown in the video below, by varying the frequency and the intensity of a recording electrode,
it is possible to assess the receptive field of the fibe.
o When the probe enters into the receptive field, the neuron increases its discharge rate (red color).
o Outside the receptive field, the activity of the neuron goes down to the spontaneous rate (blue
color).
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 o This neuron has a characteristics frequency around 4.5 kHz and a threshold around 2 dB SPL.

• A typical frequency tuning curve is shown above left. A population of tuning curves derived from
recordings from multiple 8th nerve fibers is shown above right.
o Note, the characteristic frequency (CF) is that frequency requiring the lowest amplitude stimulus
(known as the “threshold”) to excite the nerve fiber.
• As shown above right, a population, the excitatory frequency tuning curves of 8th nerve fibers extends
across the frequency range of hearing.
o This is another example of range fractionation.
• Hence, the frequency content of a sound is represented in an across-fiber coding scheme.

Two-tone Suppression
• Two-tone suppression is a nonlinear property in which the response to a particular
frequency is reduced by the simultaneous presence of a second tone at a different frequency.
• Suppression has been observed in measurements of basilar-membrane displacement and of
neural-firing rate.
• Two-tone suppression plays an important role in the coding of complex signals, such as
speech and has been suggested to result in the enhancement of spectral contrast of complex
sounds, such as vowels.

• 8th nerve fibers exhibit two-tone suppression as shown at right →

• In the top panel, a 113 Hz, CF tone is presented at 10 dB above the fiber’s threshold
(smaller, dark line).
• The cumulative response of the fiber to 10 stimulus presentations is represented by the
histogram.

• In the remaining panels, a second tone of 600 Hz (indicated by the oval) is embedded in
the CF tone and presented at increasing intensities.
• Note, that when the second tone is presented at 87 dB, it totally suppresses the response of
the fiber to the CF tone.
• Two-tone suppression is non-neural in origin.

• It is Due to destructive interference of traveling waves along the basilar membrane that
serve to decrease the magnitude of movement such as that illustrated in the movie below.

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 • If one varies the frequency and amplitude of the second tone, one can
construct inhibitory frequency tuning curves as shown in blue at left.
• This is a form of lateral inhibition that serves to sharpen frequency
selectivity.

Rate Code for Stimulus Frequency

• 8th nerve fibers discharge to tones of different frequencies with a
characteristic pattern of activity.

• As illustrated in the top panel above, for frequencies < 3 kHz

individual fibers respond in a cycle-by-cycle manner to a specific
phase angle of the waveform.
• For frequencies < 3 kHz individual fibers respond in a cycle-by-cycle
manner to a specific phase angle of the waveform. This is illustrated
in the bottom panel of the above picture.

an interspike-interval histogram. →
• It represents the interval between action potentials (the firing rate)
when an 8th nerve fiber responds to a tone presented multiple times
(shown at left).
• Note that there are times that the fiber does not respond to every
cycle, but sometimes skips one, two, even three cycles at times.

• The cycle skipping is represented by the different peaks in the

interspike-interval histogram where the first peak represents the cycle-by-cycle response, the second peak
represents the number of times a cycle was skipped, etc.
o Recall that the stimulus period (t) is inversely related to stimulus frequency (f): t = 1/f or f = 1/t.

• Using the time represented by the maximum height of the first peak of the histogram (the other peaks
are not used), it is seen that t = 2.4 msec which corresponds to a frequency of 416 Hz.

• The auditory system performs this calculation to determine stimulus frequency from the phase-locked
responses of 8th nerve fibers.
• This represents a “rate code” for stimulus frequency at the level of the 8th nerve.

Coding of Amplitude Modulation

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Shown above is the temporal envelope, representing amplitude modulation (red line), for a typical sound.

Note, the modulations occur at different rates, have different durations as well as the time it takes for them to reach
their maximum amplitude (rise time) and return to baseline (fall time).

All of these features are temporal cues that the nervous system uses in concert with frequency cues to recognize
sounds as illustrated in the figure below for the phrase, “she wiped her off with a cloth”. Note the differences in
frequency (top) and amplitude modulation (bottom) and how they are unique for each word.

How is amplitude modulation represented at the level of the 8th nerve? This is illustrated in the figure below.

All 8th nerve fibers respond to acoustic stimulation with a tonic discharge pattern that corresponds directly to the
pattern of amplitude modulation.

In conclusion, sound recognition does not take place at the level of the 8th nerve.
However, the activity of 8th nerve fibers provides the CNS with an accurate
neural copy of acoustic signals which are then processed by higher centers in
the ascending auditory pathway.

 Ascending Auditory Pathway

• As shown at left, the ascending auditory pathway characterized by both
diverging and converging neural pathways.
• This organization gives rise to both serial and parallel analysis of auditory
information.
• Significantly, with respect to sound recognition, cells at successive
levels of the ascending auditory pathway show increasing selectivity for
behaviorally relevant sounds.
• This is best illustrated by studies of the auditory system of the Mustached
Bat shown at left (YOU WILL NOT BE TESTED ON THIS).

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 • As you may know, bats use echolocation to identify and capture insects in flight.
• The signals they emit are brief and in the ultrasonic range beyond the frequency sensitivity of human
hearing.

The below video illustrates how bats utilize echolocation in prey capture.

Critical features of the bat’s echolocation signal are shown below.

The bat’s emitted echolocation signal (solid lines above) is represented by

several harmonics (1-4) each consisting of a constant frequency tone (CF)
followed by a downward frequency (FM). Features of the returning echo
are shown by the dashed lines above. Note, they are almost identical to the
emitted echolocation signal.
Significantly, at the level of the bat’s primary auditory cortex there are
several specialized regions comprised of auditory neurons that respond to
very specific features of the emitted call and returning echo.
These are illustrated below.

The FM-FM area measures the delay between the emitted pulse and returning echo
thus providing info re: distance to the target – the longer the delay, the more distant
the target.

The CF-CF & DSCF areas measures the frequency of the emitted pulse and
compares it with the frequency of the echo thus providing info re: degree of doppler
shift and therefore, target velocity. If the frequency of the returning echo is higher
than the emitted pulse, the bat “knows” that it is closing in on its prey.

Significantly, the “specialized” properties of neurons in these cortical areas are

systematically created via excitatory and inhibitory interactions at successive
levels of the auditory system.

The bat auditory cortex also illustrates a feature common to the auditory cortex of
other animals, including humans. It, like the visual cortex, is modular with respect
to its functional organization.

Sound Localization

It is not only important to determine “what” a sound is, but also “where” it is coming from.

Auditory system uses multiple mechanisms to determine both the vertical and horizontal location of an acoustic
signals.

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Vertical Plane
• As explained in the movie below, sound waves reflecting off the
uneven surfaces of the pinna and concha, as well as the rest of the
head, to produce interference patterns at different frequencies, called
head-related transfer functions (HTRFs) depending upon the position
of the sound in the vertical plane.

• These “spectral notches” are utilized by the auditory system to

establish the location of a sound in the vertical plane.
• They are processed in the same way as frequency information is
processed which was discussed previously.

Horizontal Plane
• According to the “Duplex Theory”, sound localization in the horizontal plane is mediated by two cues:
o Interaural Time Differences (ITDs)
o Interaural Intensity (or level) Differences (IIDs or ILDs)
• Both cues require a comparison of the sound signal arriving at the two ears.
• With respect to the auditory system, where and how does this comparison take place?

• The superior olive is the first auditory center to receive convergent

input from both ears.
• The superior olive plays a critical role in extracting ITD and IID
information.
• How is this accomplished?

The Neural Analysis of ITDs

• At left is a cross section through the mammalian auditory brainstem showing the superior
olivary complex.
• Lateral Superior Olive (2), Medial Nucleus of the Trapezoid Body (3), Medial Superior
Olive (4)
• The analysis of ITDs takes place in the medial superior olive (MSO; 4
above), a subdivision of the superior olivary complex.

Drawings of labeled MSO neurons are shown →. The arrow indicates the
long axis of the MSO.
• Somata of neurons are aligned parallel to the long axis of the MSO.
• Dendritic tufts extend laterally in both directions.
• Tufts on one side receive excitatory input from the contralateral cochlear nucleus.
• Tufts on other side receive excitatory input from the ipsilateral cochlear nucleus.

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 How does this contribute to ITD analysis?

The Jeffress Model explains how ITD information is extracted via the
creation of “delay lines” and coincidence detectors.

The Neural Analysis of IIDs

Analysis of IIDs takes place in the lateral superior olive (LSO; 2 in the
above cross section of the superior olive), a subdivision of the superior
olivary complex.

• EI cells are created in the LSO.

• EI cells are excited by ipsilateral input, inhibited by contralateral stimulation.
• Output of EI cells varies with location of sound source in the horizontal plane.
• Comparison of EI cell activity in the right and left LSO nuclei provides accurate information about the
location of a sound source in the horizontal

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 Maps of Auditory Space
• Spectral notch information is represented by the activity of neurons in the
cochlear nucleus.
• ITD information is represented by the activity of neurons in the MSO.
• IID information is represented by the activity of neurons in the LSO.
• Information carried over these three pathways converges on neurons in the
inferior colliculus creating maps of auditory space.

• As shown above, individual neurons in the inferior colliculus have

spatial excitatory receptive fields with respect to the location of a
sound source in the horizontal and vertical planes. At left is the
spatial excitatory receptive field of a neuron that will respond only
to sounds from +40 to -30 degrees of elevation, and approximately 10 degrees left to 25 degrees right.
• All areas of auditory space are mapped.
• Collectively, these cells create a “map” of auditory space in the inferior colliculus that is used to identify
the location of a sound source.
• Thus, auditory space in the inferior colliculus is represented by an across-fiber coding scheme.

• Similar to visual cortex, there are several subdivisions of the auditory

cortex, shown at left) involved in sound analysis.
• These regions integrate frequency, time and spatial information derived
from activity in lower auditory structures to construct an “image” of the
auditory environment in terms of “what” and “where”.

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