Unit 1 - Lecture 2 Flashcards
What are the details of the travelling wave? Effect of sound level on what?
- Bekes’y early finding
- Modern tech and active component
- Effect of sound level on tuning and peak shifting
- Behaviour test for level-related peak shifting
Determining factors for BM vibration - stiffness gradients
Stiffness determined by BM width and thickness
Determining factors for BM vibration - mass gradients
Mass determined by the size of organ of Corti
Determining factors for BM vibration - effect
Phase/time delay of different value
Determining factors for BM vibration - results
BM vibration as traveling wave from base to apex
Bekesy’s measurement of BM displacement
- how did he observe the traveling wave?
- what was freq. limited to?
Bekesy Worked in telephone company to design telephone/ earphone
Led to his 1928 discovery of mechanical vibration of inner ear
Dissection of cochlea
Observation of traveling wave using stroboscopic device on motion of silver particles.
Limited to fre. <1600 Hz
What is the direction of the travelling wave?
base to apex
What is the peak location of the travelling wave?
The natural frequency
The travelling wave is an ____ envelope
asymmetric
The travelling wave is ____ for ____ frequencies.
broader, low
The travelling wave speeds up toward the ____ then fades away.
peak
What two things is the travelling wave not equal too?
signal frequency and sound speed
Why does vibration travel?
- Mass gradient***
- Larger mass = larger time delay (slower response)
- Cause phase delay varied along cochlear duct
What is not the reason of vibration travel?
- Not due to sound getting into cochlea via stapes
- Evidence? If we apply the sound source to the apex the traveling wave still occurs and travels from the base to the apex
o Sound travels faster in water/fluid so it doesn’t take long for the sound to travel the whole cochlea
o Traveling wave is faster at high freq. and slower at low freq. region
o Faster the traveling wave the better the synchronization
What component did Bekesy not include?
The active component
Explain the importance of the active component
- Active component is dominant at low sound level. Passive one is dominated at high levels
- Overall amplitude of active component is smaller than the passive one at higher sound levels.
- Active m. require healthy cochlea
2 and 3 make the active component more difficult to record
Active component is OHC
What is required for measuring the active component?
- living, healthy OHCs
- low sound level
- highly sensitive equipment
BM response in dead and living cochlea (pic 1)
Black lines: responses of dead cochlea
Red lines: responses of living (healthy cochlea)
At low sound level, cochlea with healthy OHCs shows sharper tuning, larger amplitude in its BM vibration than the dead/passive cochlea
At high sound levels, the BM vibration is similar between healthy/active cochlea and dead/passive one
Passive = black line (small but goes to larger areas)
Active = red line is localized
Don’t know the active component when the sound level is high
What are the 3 methods to observe BM vibration?
- capacity probe
- mossbauer technique
- Laser doppler interferometry
Capacity probe
- Capacitor: two conductive plates separated by a non-conductive layer
- The probe serves as one plate, BM the other one
- Dry air in between is the insolation.
- BM vibration change the distance between the two plate and therefore the capacitance change.
- Require water to be drained, bad for cochlea
- Sensitivity is poor
Mössbauer technique
- Doppler effect: signal frequency changes by the relative speed between the generator and receiver (when you hear an airplane it sounds high pitch then the pitch becomes lower, however the pitch isn’t changing)
- radioactive material applied to BM to produce signal of known frequency
- Receive test vibration of BM by measuring the frequency change
Laser Doppler Interferometry
- Doppler shifting from light reflection (from applied glass balls, or from cellular fat)
- Most modern method
- A laser beam is applied
Where is surgery easiest?
- Easier at basal and apical ends
- measurement is limited to basal and apical ends
- apical end and round window are the 2 things that produce the minimum emission damage to ensure the health of the cochlea
Pattern versus point
Point Test
- Point test requires smaller surgical opening, therefore smaller damage
- More practical
- In point test, signal frequency is changed, and the probe location is fixed
- How do we get overall pattern from point test? Accumulate results from hundreds of animals
- Put all the points together and get the pattern
Pattern Test
- Overall pattern of vibration can be elicited by test at multiple points, from multiple subjects.
- In pattern test, probe location is changed, not signal
Displacement versus Speed (velocity)
Vibration at high frequency cannot have large displacement; therefore, amplitude is small.
Velocity test is fair to compare across different frequency regions.
BM frequency selectivity in point test: two types of curves
Iso-intensity-amplitude curve
Frequency-threshold curve
Iso-intensity-amplitude curve
how amplitude change with frequency at the same sound level
CF is the peak in the tuning curve
Best frequency matches the CF
Largest vibration is produced by a lower frequency (lower than CF) – because of travelling wave
Frequency-threshold curve
Similar to tuning curve
Key point to remember in point tests
The test is done at a fixed location, so the results are vibration that can be seen at this point. Stimulation varies in intensity and frequency.
Frequency selectivity of receptor potential
- Basilar freq. (BF) changes seen in receptor potential
- BF shifts to low freq. at higher intensity
- Increasing sound level –> shift to low freq. side/point
Gain changes with ____ level
sound
Explain gain and vibration in correlation to sound level
If sound level is 3dB SPL, gain can go up very high (lower the sound level, larger the gain)
When sound is high, gain is reduced
Gain reduces with sound level, although vibration amplitude (here is measured as speed) increases with intensity. “Best frequency” shifted downward to low frequencies in both graphs.
Tuning becomes wider with an increase in ____
Sound pressure level (SPL)
BF shifts to low frequency with increase in ____ at a fixed point
Sound pressure level (SPL)
A low frequency signal produces a vibration that is spread to…
higher frequency region at high sound level
What does BM vibration look like over the whole cochlea but by a fixed frequency?
- The overall vibration across cochlea can’t be directly measured
- Cochlea integrity will be lost if we open the shell too much
- The overall view of the vibration must be obtained from multiple points
- Vibration by a fixed frequency across levels
Explain a point test
The result of point test, showing the vibration seen at a fixed point (with CF 10 kHz) in response to sound of different level and frequency.
Freq. decreases with sound level
In point test, BF decreases with increased sound level
Explain a pattern test
The vibration pattern by testing at multiple sites in response to a tone of fixed frequency (14.5 kHz) but different levels.
Freq. increases with sound level
In overall pattern: vibration peak shifts towards basal end (higher frequency
Are point and pattern conflicting?
Yes
This is the test of ____ is not fair for evaluating vibration at high freq.
displacement
Why is there a peak shift?
From acoustic trauma
Explain acoustic trauma
- Applying 4kHz tone at high intensity
- TTS (temporal threshold shift) and PTS (permanent threshold shift) are maximal at 6 kHz
- So as the hair cell loss
- Half-octave Law
- Hearing loss produced at 4k tone shifts to high freq. region
Noise induced hearing loss is the half octave law (largest damage occurs half octave above the freq. of noise exposure)
BM response in dead and living cochlea - Low sound levels
At low sound level, cochlea with healthy OHCs shows sharper tuning, larger amplitude in its BM vibration than the dead/passive cochlea
BM response in dead and living cochlea - High sound levels
At high sound levels, the BM vibration is similar between healthy/active cochlea and dead/passive one
Time interval allows BM vibration to be ____ and therefore the use of ____.
reduced, low-level probe
What are the main points stimulation of HC and cochlear transduction
- BM vibration to shearing or bending
- Bending of stereocillia to open ion channels
- Current (carried by potassium) to potential
- AC vs. DC response
- Ion channels involved
- Behaviour or receptor potential is nonlinearity
Do the OHC touch the tectorial membrane?
The tallest sterocillia in OHC are embedded in the tectorial membrane
Different ways for hair bundle bending between IHCs and OHCs
OHCs are embedded in the tectorial membrane
Hair bundles on IHCs are not embedded in TM
Bending is driven by Hensen’s strip and hydraulic force
How many rows are there of OHC?
3 rows
Explain the difference between IHC and OHC links
The links across the stereocilia of IHC are not as strong as OHC (people think the stereocilia of IHC are freely vibrating alone)
Different OHC links
Three types of links:
1) Row-to-row
2) Side-to-side
3) Tip-to-side (tiplink)
1) And 2) are thicker, they hold the stereocilia together, control the stereocillia in groups
3) Control MET channels
Stereocilia on IHC are driven by ____, there are no strong row/side links
hydraulic force
Why is it good that the IHCs are free of strong links?
Being free of strong links across the stereocilia make them easier to bend in response to hydraulic turbulence
Explain the battery theory
In order for the HC to function as a receptor (to produce receptor potential) there are 2 batteries that are connected.
The more powerful one is on the surface of the scala vascularis, the smaller one is on the individual hair cell (which makes the intracellular potential negative -60mv)
The battery from the SV makes the SM +80mv
Together, the total is 140 mv (favours the movement of potassium from SM into hair cells)
Explain the standing current
Current when there is no stimulation
Always baseline opening of MET channel and small amount of potassium diffusion across supporting cells & BM
Standing current: goes from SV, SM, organ of corti, perilymph, and back to SV (or SV, across BM, and back to SV)
Nothing to do with sound, happens without sound stimulation
Largely occurs across OC (not a waste of energy)
Transduction channels
Location: inside the stereocillia
Ion selectivity: not selectivity
Gating function: controlled by tip links (voltage, light, temperature, pressure, force), mechanically gated which is controlled by the tiplinks
What does the Holt and Corey PNAS model propose?
That a channel is located around the tip, but also the side of the stereocillia
The entrance of MET channels are likely located at the ____ of tip link on the shorter stereocilia.
root
What is CDH23?
Gene that has been recognized as a gene in animals for aging related hearing loss (this gene has not been found in humans), only partially related
Summary of ion channels involved in HC functions
- Bending to excitation causes opening of MET channel, this opening is controlled by calcium (calcium can also pass the MET channel) – MET cannot remain open for a long time
- Intracellular potassium level increases (potassium channel is voltage gated) – there is no link between calcium and potassium channel on lateral wall
- Calcium triggers the release of NT
Sequential events in HC response to sound
Deflection—transduction channel opening, transduction current increase
K inward—depolarization
ICa increase causes:
- IK increase—repolarization
- Neurotransmitter release
AP of auditory N
Stereocilia deflection & receptor current
No deflection: standing current balanced by outward current-resting potential
Deflection towards kinocilium (laterally in cochlea) increases inward current –> depolarization and cause 8th firing
Deflection towards modiolus (medially), decreases inward current (hyperpolarization)
Hair Bending Receptor Potential
Depolarization and hyperpolarization periods are very short
Depolarization = higher chance of AP
The impact of frequency on receptor potential - AC component
The AC component amplitude is decreased with increasing frequency:
- Due to capacitance and resistance of the membrane: low-pass feature
- Due to the low-pass feature of recording electrode
- How this impact OHC motility?
The impact of frequency on receptor potential - DC component
The DC component amplitude is increased with frequency
- During the stimulation, K is accumulated inside HCs,
- This is more significant when signal frequency is high, due to lack of time to remove K.
Nonlinearity in CM response-level function
Noting that the dynamic range for CM is larger than that of typical range for auditory nerve, suggesting that the cochlear compression is not fully established at CM level but at the active feedback from OHCs to IHCs.
By increasing sound level from low to high, CM amplitude increases then saturates when sound level is very high
OHC functions as an amplifier
Key points of cochlear nonlinearity
- how is it shown?
- where does it originate?
- what does it depend on?
- what is it vulnerable to?
- what does it require?
Shown in different ways: response-level function; distortion products in OAE
Originates from inside cochlea
Depends on active mechanism
Vulnerable to damaging factors
Requires intact OHCs
Where does nonlinearity occur?
Nonlinearity occurs in a restricted area around CF, where rapid increase was seen at low-moderate intensity; saturated at high level.
Linear growth at freq. away from CF
Cochlear amplification (what is it from and what does it do)?
From OHC motility
Provides sharp tuning (?)
- Don’t see motility showing any sharp tuning or freq. selectivity, so we don’t know why HC at different location show different freq.
Provides high sensitivity
Explain what happens during BM vibration at low sound level in active and passive cochlea
Active component by OHC increase the sensitivity and tuning
Vibration from low level sound in passive cochlea is so small it cannot be detected
When HCs are excited they become ____.
shorter
Amplitude difference between BM and RL is larger at ____ sound level
low
Amplitude difference between BM and RL
Theoretically, the difference in amplitude between BM and RL can be considered as the gain by OHCs, which is larger at low sound level.
Where is sharp tuning seen?
Sharp tuning seen in receptor potential, BM vibration and auditory nerve
No need for second filter
Or OHC motors are second filters
Sharp tuning and nonlinearity depend on ____
OHC
OHCs as motor (comes from what 3 lines of evidence)?
Comes from 3 lines of evidence
1. Dallas: OHC lesions elevate threshold
2. Brownell: OHCs motion in response to voltage changes
3. Many researchers: OHC motility contributes to cochlear amplifier
Receptor potential activates motors
Motor must be something that can be electrically driven
Types of OHC motility
Fast motility of OHC bodies (mostly understood & responsible for active mechanism)
Slow motility of OHC bodies (refers to shift change in response to ion change - not main concern & does not contribute to active mechanism)
- K+, Ca++, and ATP
Motility of hair bundles (not seen in mammal cochlea)
General feature of fast motility of OHC body
- what does it follow?
- why is it different from muscles?
- how is it driven?
- length change?
Fast: follows hearing frequency range
Different from muscles: independent of ATP and Ca++, does not require muscular proteins (actin and myosin)
Fast motility is driven by voltage difference across cell membrane
Asymmetric length change up to 5%, without volume change
What are 2 methods for recording fast motility?
whole patch and microchamber
Fast motor
A protein in plasma membrane
Prestin is rich in OHC, not in IHC
Gene: SLC26A5
Prestin appears at the same time as ____ after birth
OHC motility
Prestin is related to ____
fast motility
Explain fast OHC body motility
- what is it proportional to?
- how fast can it flow?
- how much does the length change?
Proportional to MP (membrane potential) changes
Fast: flows up to 20 kHz
Length change up to 5% - 1-5 um, comparable to BM vibration by sound
When hyperpolarized, protein moves ____, when depolarized, protein moves ____.
in, out
When HC moves medially it ____, when HC moves laterally it ____.
elongates, shortens
How does OHC motility enhance stimulation to IHCs
Not clear
Maybe by hydraulic turbulence
Maybe by changing the interaction from tectorial membrane (shortening of IHC length may pull the tectorial membrane closer to reticular lamina)
No methodology can ensure a reliable observation in this small area
How OHC length change impacts coupling to IHCs?
OHC shortening reduces the distance between IHC and TM
What is the structure of prestin at high frequency?
AA for high frequency
How the gain is changed over sound level
- Larger gain at low sound level
- Smaller gain at high sound level
- We don’t know if the motility of OHCs saturate with increasing sound level
- The response of IHCs and ANFs becomes saturated at high sound level. Do they related to the automatic gain control?
How is the cochlear amplification/motility tuned?
- Electrical resonance of HC (not in mammal)
- Mechanical resonance of BM
- Tonotopic differences in the stiffness of hair bundles.
HCs in amphibians, reptiles and birds are tuned (electrically), not seen in OHCs of ____.
mammals
Motility of hair bundle
- what animal shows best frequency
- what does oscillation follow?
- what drives hair bundle to move?
- The electrical resonance in turtle HCs shows best frequency (turned)
- Oscillation following membrane potential
- The electrical resonance may drive hair bundle to move
Mechanism for amplification tuning in mammals (are OHC sharply tuned)?
- OHC motility is not sharply tuned
- The sharp tuning of BM by OHCs is not fully understood.
o “initiated” from BM passive tuning
o From hair bundle motility? - Hair bundle motility is seen in amphibians, not in mammals
- Is it possible?
New evidence for hair bundle motility in mammalian cochlea
- In mammals, stiffness change with deflection
- More recently, length change
Is there hair bundle motility in mammals?
- It is likely, but no evidence yet
- If not, cannot explain frequency selectivity of OHC amplification
- But the evidence is not solid yet.
