So I'd like to now give you a broad overview of the function of this part of the inner ear. So we have a little region right here that's called the oval window, and this Oval window is the site where the Stapes makes contact with the inner ear. So you recall that the Stapes is the, most proximal of those 3 inner ears ossicles and it functions like a little piston that moves back and forth, back and forth, providing pressure on the inner ear at the level of the Oval window. And that's the Stapes bulges into that Oval window, pressure waves are transduced into the fluids that run in the Scala Vestibule and the Scala Tympani. And these fluids are then conducted along the entire length of the Cochlea. from this site of inward protrusion here in the Oval window. And then eventually, that pressure is relaxed with an outward bulge at the round window. And along the way, there are vibrations that are set up along this Cochlear partition. From the base of the Cochlea all the way up through its Apex. These waves of pressure that are conducted through the fluids that run through the Cochlea, then, will cause a vibration to happen within this Cochlear partition. And that vibration then will cause a mechanical deflection of those tiny Silia at the tips of the hair cells and this will be key for the transduction of this energy in to electrical signals. Now what I'd like to do next is to talk about the tuning properties of this Basilar membrane. And one convenient way to do it will be to uncoil this Cochlea and stretch it out flat and have a look at the properties that exist across the length of that Basilar membrane. So that's what we've done here. this is a representation of the human Cochlea. So here's our Stapes pressing back and forth against the Oval window. Here's the round window where that pressure is commensurately relieved. And now I think we can better appreciate how pressure waves might travel from the Oval window out to the Round window. With this point of continuity at the tip of the Cochlea which was, which is called the Helicotrema. So on the superior side we have the Scala vestibuli, on the inferior side the Scala tympani. And what the movement of the Stapes does then is, sets up a traveling wave that causes the Basilar membrane to vibrate up and down as these waves are conducted throughout the Cochlea. And it's this movement of the Basilar membrane, specifically the movement of the Basilar membrane against the Tactorial membrane that causes the hair cell Cilia to move one way and then the other. Now as we look at this Cochlea unwound we need to appreciate some of the bio-mechanical properties of the Basilar membrane. Brain that allow for that important function to be performed, that is the decomposition of complex sound into component frequencies. So near the base of the Cochlea, the basilar membrane is considerably thicker. And stiffer, than what we find at the apex. At the apex of the Cochlea, the Basilar membrane is broader, and it's much thinner. Than what we find at the base. And, this gradation we find between the base of the Cochlea and the apex allows the Basilar membrane to map out in a smooth progression tone. With high frequencies being represented near the base of the Cochlea where the Basilar membrane is much stiffer. And it will vibrate best at high frequencies, compared to the apex of the Cochlea where the Basilar membrane is much more pliable and vibrates best to low frequencies. So if we looked at, for example, positions one and two here near the base, we find higher frequencies that give rise to the greatest amplitude of vibration. Whereas positions six and seven now vibrate best, with greatest amplitude with Low frequencies of stimulation. Now, in addition to these biomechanical properties that establish this important Principle of Tonotopy, or frequency mapping in the Auditory System, there are active mechanisms that involve the Outer hair cells that fine-tune. The way this coupling works between the Basilar membrane and the Tectorial membrane. If we look then at this organ of Corti, in the Cochlear partition. what we see is contact between the Tectorial membrane and this organ of Corti, this Sensory Epithelium. And the contact is in the form of these Sterocilia that grow out of the Apex of these hair cells. These Outer hair cells. They're innervated. But they're actually innervated by Axons that have an efferent signal. So we can think of them as being motoric in nature. The motor is actually in the hair cell itself. So what these hairs cells do is they can contract, and extend and as they do so they change the stiffness of their contact with the Tectorial membrane. And this active mechanism then allows for the vibrations to be fine tuned by the central nervous system. Meanwhile, the Inner hair cell is innervated by Sensory Fibers, that have grown out of the Spiral Ganglia. That sits near the axis of rotation of this Cochlea. And these sensory endings, then, will receive the electrical signals that are generated here in the Inner hair cells. So, let's now see how this all works. So, as traveling waves run through the Scala vestibuli, around the Helicotrema into the Scala tympani, this Cochlear partition begins to vibrate up or down. And because of the pivot points of these two Membranes are offset relative to the center of the Cochlea. What we find is, a Shearing force develops as this Cochlear partition rises upward and then recesses downward. This Shearing force deflects the Stereocilia at the tips of these hair cells first in one direction. And then in the opposite direction. So with each up and down cycle, there is a wagging back and forth of these Stereocilia at the Apex of the hair cells. And that movement of the Cilia will open and close ion channels that allow ions then to enter the tips of these Stereocilia and generate graded potentials in the Inner hair cells. So let's now talk about how Sensory transduction actually works at the tips of these hair cells. So as I mentioned earlier, there is a third channel that sits in this Cochlear partition and it is quite special. It has a different kind of media in it compared to what we find in our Scala vestibuli and our Scala tympani. In those two larger channels. The solution that we have there is called Perilymph and Perilymph is very similar to the solution that based most of the cells of our body. it has a relatively low concentration of Potassium and as you now know quite well, within nerve cells Potassium is concentrated to quite high levels. Now, the Scala media is really distinct in this respect. It has very high levels Potassium. This Endolymph is enriched in Potassium because of the activity of cells in a highly Vascularized Structure that has extremely high metabolic activity. It's called the Stria vascularis and this is an Epithelium that secretes Potassium and concentrates it within the Scala media. Now why is that relevant for Sensory transduction? So here is an Inner hair cell, and its Stereocilia are protruding off the Apical surface of the organ of Corti, that Sensory Epithelium, and at the very tips of these Stereocilia are Potassium channels. And the Potassium channels from one Stereocilia to the next are connected with a spring-like protein called a tip link. And what that protein does is it connects a gate that is on the Extracellular side of this Potassium Channel, from one Stereocilium to the tip of an adjacent Stereocilium. And as a result, as these Stereocilia wave in one direction, the tip links are stretched, and that transduction gate is opened. And when the gate is opened, then Potassium ions can rush down their concentration gradient because remember, Potassium is concentrated to very high levels here in the Scala media. So as Potassium enters through these Potassium Channels at the tips of the Stereocilium, the hair cell will depolarize. And a graded potential is established in that hair cell with the influx of Potassium. That potential eventually opens up Voltage-gated Calcium Channels That exist on the sides of these hair cells. So now, not only does Potassium enter through the apical surface of the hair cell, now Calcium rushes in through the Basal lateral aspects of the hair cells. And as Calcium enters, then a Calcium dependent Exocytosis of Synaptic Vesicles occurs along the Basal region of the hair cell. Essentially, Neurotransmission occurs. A Neurotransmitter then is secreted from these Vesicles. And makes contact with receptors at the peripheral and of the spiral ganglion processes. So this afferent nerve here then is receiving synaptic connection from this Inner hair cell. And with the release of transmitter binding to receptors, ionotropic channels open up, and cations rush into that afferent nerve terminal, and an action potential is generated that may then propagate into the brain. Now, what I've described for you is what happens when the stereocilia are deflected In a particular direction towards the longest Stereociliam, that's the deflection that puts stress on the tip link. Pulling open that transduction gate allowing for Potassium to flood into the Stereocilia. Well, I mentioned that these cilia will move back and forth with the upward and downward of deflection of the Basilar membrane. As these Stereocilia then relax back and are bent in the opposite direction, away from the tallest Stereocilium. Then the stress on those tip lengths is relaxed and the transduction gate can then close over the top of the pore of the channel. So, the movement of these Sterocilia allow for the cyclical opening and closing of this transduction gate, and one can imagine, then, what would happen to the membrane potential. The membrane potential would rise, would depolarize as the Stereocilia are deflected towards the largest Stereocilium and then the membrane potential would fall or hyperpolarize. As those tip links are now relaxed, the gates close and Potassium no longer rushes in.
