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Introduction To Hearing
Introduction To Hearing
Must-See Websites:
Journey into the world of Hearing
(http://www.cochlea.org/en/spe)
R. Keith Duncan
University of Michigan
rkduncan@umich.edu
Reviews:
Gillespie et al. (2009) Cell, 139:33-44
Nouvian et al. (2006) J Membrane Biol, 209:153-165
Fettiplace and Hackney (2006) Nat Rev Neurosci, 7:19-29
Outline
Sound transmission
The identity of sounds is conveyed largely by their frequency content. The cochlea
analyzes sound for frequency content, mapping frequency and energy level to a specific
place and transmitting this along with timing to the CNS.
spectra of the
sounds coming
out of the mouth
spectrum of the sound
produced by the glottis
Helicotrema
1.
2.
3.
4.
5.
Cochlear Partition
Scala Vestibuli
Scala Tympani
Spiral Ganglion
Auditory Nerve Fibers
TM
1. Scala media
2. Scala
vestibuli
3. Scala
tympani
4. Reissners
membrane
5. Basilar
membrane
6. Tectorial
membrane
7. Stria
Vascularis
8. Auditory
Nerve
9. Bony Spiral
Lamina
HeC
PC
DC
BM
Reticular
Lamina
Driving
Force
For
Potassium
How do we know that hair cells are the transducer elements for hearing?
(1) innervated, (2) loss associated with deafness
Inner hair cells are primarily responsible for transmitting sound stimuli
because these receive 95% of primary afferents and are more tightly
associated with profound deafness.
In mM:
145 Na+
3 K+
130 Cl1 Ca2+
Endolymph
+80 mV
In mM:
5 Na+
160 K+
130 Cl~ 0.02 Ca2+
-60 mV
0 mV
Hair Bundle:
Staircase (pipe-organ) of
actin-filled microvilli called
stereocilia
Bilateral symmetry
Stereocilia tapered at base
Tilted inward
Stereocilia interconnected
Kinocilium (true cilium) not
present in mature cochlea
of mammal
IHC
OHC
Turtle VHC
Bullfrog VHC
Turtle VHC
From Geisler text
Functional differences in
bundle shape?
Stereocilium Structure
Tilney et al.
(1983)
Transduction: Methods
Semi-intact preparations are used for
whole-cell patch-clamp studies.
Hair bundles stimulated with stiff
probes or water-jets.
Voltage-clamp:
Constrain voltage
Measure current
Probe
Used to determine voltage
dependence
Patch
Pipette
Current-clamp:
Inject current
Measure voltage
Used to measure action potentials
and receptor potentials
Transduction: Directional
Shotwell et al.,
1981
Gentamicin (aminoglycoside
antibiotic) used as open channel
blocker of transduction channel.
Jaramillo & Hudspeth, 1991
Freeze
Etch
EM
50 nm
Surface
Rendering
Note: At this point, it is still unclear whether the tip-link can be the stretchy element..
Note: Transduction channel now known to be at the other end of the link.
TRP?
New possibilities?
P2X?
Tmc1/2?
Adaptation Models
Displacement Stimulus
fast ~ 0.1-1 ms
(slow, ~ 20 ms)
(fast, <1ms)
slow ~ 10-100 ms
Fast adaptation: due to a Ca2+ dependent channel closure ( ~ 0.1 ms)
Slow adaptation: depends on mysoin, ATP, and Ca2+ ( ~ 10 ms)
Motor models of slow adaptation include myosin-dependent
climbing/slipping of the upper tip-link density. Tension established
by this process sets the resting open state of MET channels (Po ~ 0.1)
Open Questions
Mechanoelectrical transduction
initiates a change in receptor potential.
Basolateral condutances set the
resting potential, shape the receptor
potential, and govern synaptic
transmission.
Measure amp. of
motion for constant
input pressure at
various frequencies.
1 kHz
250 Hz
Passive mechanics largely
due to gradual changes in the
stiffness of the basilar
membrane.
Base: thick and narrow
Apex: thin and wide
Displacement (nm)
If you double the input to the basilar membrane, the output less
than doublesat some stimulus levels.
Linear growth
1 dB/dB
Basilar membrane
Distortion is a key feature of
nonlinear systems. All combinations
are generated (n*f1 m*f2) but cubic
(2f1 f2) is largest.
Cubic Distortion
Loss of OHCs
+50 mV
OHC Motility
-150 mV
IHC
OHC1
OHC2
OHC3
Resonant frequency,
transduction kinetics,
and hair bundle
stiffness changes with
hair cell position
along cochlea.
Attempts at synergy
Stimulus
Added
Energy
Supplementary Information
Open questions
Adornment
Protect eardrum from foreign objects
Cerumen (antimicrobial moisturizer)
Collect sound
Resonator (20 dB gain at 2.5 kHz)
Sound localization cue
Lever Ratio
malleus
incus
Area Ratio
Oval
Window
sound
waves
Area = A
Ear
Drum
Area = 20A
Electrocochleaography
Cl
Cochlear microphonic
10
C = eA/4pd.
Q(Vm )
Cm
dQ
dVm
Qmax
1 e (Vm V1 / 2 ) / )
Plot the shape
of the derivative.
11