CNS sensory and motor (Lecture 7):
Motion of basilar membrane is frequency dependent
• It turns out that the basilar membrane is critical for the transduction process. This
membrane vibrates up and down, while the oval window is being pushed back and forth
on the top and the round window moves correspondingly.
• The location of vibration on the basilar membrane is a function of the frequency of the
sound. The basilar membrane is stiff near the oval window and as we get farther away
from it, the membrane gets more flexible.
• Low frequencies vibrate towards the end of the basilar membrane, away from the oval
window. High frequencies, on the other hand, vibrate closer to the oval window.
• If we have a mixture of frequencies, we have vibrations at different places.
• What the basilar membrane is doing is extracting the frequency of the sound. In a 1kHz
sound, the time these pressure waves flow by your head is every 1 milisecond.
• Remember this is the cochlea which we’ve unrolled.
The basilar membrane in action
Video of a computer model of the basilar membrane. The model
was made by a researcher named Dr. James Hudspeth, from
Rockefeller University. Over the last 20 years, he has been one of
the leaders at revealing the transduction process of the auditory
Basilar membrane motion is converted into neuronal activity at the organ of Corti • Cochlea, all round up, is presented in blue. If we take a slice through the cochlea, we see
three fluid-filled chambers. The middle one, the cochlear duct, has the organ of Corti
sitting on the basilar membrane. This is where the transduction process occurs.
• So, what happens when the basilar membrane moves up and down?
Deflection of basilar membrane produces shearing of hair cell sterocelia:
• We first have to notice that there a four rows of specialized hair cells, which are the
receptor cells where the transduction process occurs.
• These four rows run down the length of the cochlea. There are only about 50 000 hair
cells per cochlea, which there are 100 million photoreceptors in the retina.
• These cells are called hair cells, because they have a little tuffed stereocelia that sticks
out at the top. These hair bundles (sterocilia) stick up into the tectorial membrane, sitting
right on top.
• There are three rows of outer hair cells.
• Inner hair cells & outer hair cells have slightly different functions, but we will not
distinguish between them.
• As the basilar membrane goes up and down, the motion between the basilar membrane
and the tectorial membrane is
a little bit different. This
difference produces a shearing
force that causes the
stereocelia (hair bundles) to
move back and forth. When
the basilar membrane goes up,
stereocelia bend one way.
When the basilar membrane
goes down, they move the
other way. • At a given frequency of sound, the basilar membrane is vibrating at one location, so we
are only wiggling the stereocilia of a few
hundred hair cells.
Hair cells contain mechanoreceptors:
• Through electrophysiology, by putting tiny
electrodes on the surface of hair cells, we
push the stereocilia back and forth and try to
figure out what’s going on.
Movement of hair cell stereocilia:
• Dr. David Corey, Harvard Medical School
• Movement of stereocilia back and forth with a
• First image: hair bundles. The stereocilia are
short and get longer and longer.
• Where are the ion channels? Maybe at the base of the stereocilia? It turns out they are at
the tip of the stereocilia.
• Notice in the video that as you push the hair bundle in one direction, the distance between
the tips gets closer together, and then farther apart when pushed back.
• There is something about the stereocilia (+ the fact that we’re going from short to long)
which is the key to the transduction process.
Tip links connect each stereocilia:
• Between the tip of the shorter
stereocilia and the longer one, there
were tiny and fragile molecular strings
connected the different hair bundles
(seen on second image). These tiny
molecular threads are called tip links.
• It was noticed that as the hair bundles
(the tips) go in one direction and the
distance between the tallest and shorter
stereocilia get farther apart these tip
links get pulled. • As hair bundles move in the other direction and the tips get closer together, there is less
tension on the tip links.
Tip links gate ion channels in the stereocilia:
• In the auditory system, the vestibular system has a mechanically-gated transduction.
• The molecular string
(represented as springs being
stretchy) is attached to ion
• As the hair bundles move
towards the tallest stereocilia, the
tip link gets pulled and stretched,
ultimately opening one ion
channel at a time.
• There are perhaps 20 stereocilia
per hair cell/bundle, so there isn’t
a lot of tip links and ion
• The reason it’s designed this way
is because, when we are born and
the hair cells are new (we haven’t listened to our ipod yet), you can detect pressure waves
that are just above the ambient random motion of the air molecules. => This mechanism
was devised by nature to be super sensitive.
• Because pressure waves fly past our head very quickly at 1kHz per ms (distance between
the peak at high pressure and the next high pressure). We could also hear 10kHz in less
than a ms.
• So you don’t need a G-protein cascade which takes 10s or 100s of miliseconds to get
activated the way the visual system is. We need something faster and this is why we have
this pushing and pulling of the hair bundles and tip links.
Mechano-transduction at tip link activates afferent neurons:
• As we push the hair bundle towards the tallest stereocilia, the tip links pull open the
channels and potassium enters which causes a depolarization of the hair cells. This
triggers the normal processes associated with depolarization: voltage-gated channels
allow calcium to come in, which releases neurotransmitters, and then there are afferent
neurons that then fire theAPs. Note that the hair cells do not fireAP.
• When the stereocilia go in the other direction, towards the shorter one, they come closer
together and the tip links become floppy, and these mechanically-gated ion channels
close andAP stop.
• Something is wrong: potassium is entering the stereocilia. That doesn’t happen:
potassium flows out of neurons. When it flows out, it causes the hyperpolarization and
not depolarization (?).
• It turns out that the cochlear duct (middle compartment) has extracellular fluid that is
much different from regular extracellular fluid. Specialized fluid with a high potassium
concentration. o Normally, in extracellular space, there is more potassium inside the cell than
outside, but here the potassium concentrations are reversed. (REVERSAL
POTENTIAL = Nerst potential). Same reversal potential.
• Ears are ringing after going
out of a club: this might be
because you blew up some
of the stereocilia, so tip
links have become
disconnected and start
flopping around. Then,
stereocilia grow back and
tip links “sort of” reconnect,
but not perfectly.As you
keep blowing up tip links, it
is thought they don’t
reconnect properly anymore
– they quit function. Or the
stereocilia, being fragile,
become broken and disconnected.
• The things that make our auditory system so sensitive are what you damage under loud
• There exists a condition where the ringing doesn’t stop. Some people have to have their
afferent neuron to stop it. We don’t know what causes it? Is it due to central mechanisms
in the brain stem or due to factors associated with the transduction in hair cells? Loud
noises or certain antibiotics can kill hair cells!
Visual versus auditory transduction:
• Photons are very high to catch but have
a lot of energy, so we need trillions of
opsin molecules stacked up on these
discs in photoreceptors just to catch
one! Once you get one, you can use its
energy to trigger a G-protein cascade.
• Sound waves are low energy: just
above the random movement of
molecules, but they are all around.
Pressure waves are easy to catch. So
we just need a few hundred thousand
tip links in the cochlea to hear as
opposed to trillions of opsin molecules.
• In the visual system, the photoreceptors use a G-protein cascade that slowly closes the
sodium channels (takes 10 to 100 ms = ok, since we are not moving at 500 miles per hour
and visual information is relatively constant on the time scale of a few hundred ms).
• However, pressure waves fly past our head very fast and they’re gone. So, we need
something very fast that would directly activate channels.