So, in the previous lecture, we talked about the inner ear anatomy. Let’s continue by talking about the physiology of the inner ear, in this lecture. So here’s a schematic illustration of the three compartments on the inner ear: the scala vestibuli on the top, the scala tympani on the bottom, and, between them, in the membranous labyrinth, we’ve got the scala media. Again, the compartments are made by this Reissner’s membrane on the top and the basilar membrane on the bottom. So what’s important is this Organ of Corti that’s lying on the top of the basilar membrane with its hair cells, the inner hair cells towards the medial edge and the outer hair cells. Here, we are seeing the auditory nerves enter from the central core of the cochlea and reaching out to the hair cells. There is two important structures that I want to note in this anatomical figure: we’ve got the spiral ganglion over here, the spiral ganglion refers to the collection of nerve cell bodies, and another important structure is the stria vascularis, that’s over here, and the stria vascularis refers to a group of capillaries (blood capillaries); they’re the ones responsible for producing the endolymph, which is in the scala media, and they’re also responsible for maintaining the electrical potential within the scala media, known as the endolymphatic potential, something that is going to come into play when we talk about the physiology. Again, we’ve got the tectorial membrane that kind of sits or hovers on the top of the hair cells. The tectorial membrane in mammals is such that the outer hair cell stereocilia are embedded into the tectorial membrane. And then we’ve got the basilar membrane. So in the middle ear, when the tympanic membrane vibrates because of the incoming sound, it starts that chain of action by stimulating the ossciular chain. Which, in turn, results in the footplate of the stapes pluging in and out of the oval window. When that happens, the fluid in the scala vestibuli, which is in contact with the oval window of the inner ear, it results in this fluid moving in a wave-like pattern which we call as a traveling wave because this wave travels along the length of the cochlea, all the way to the apex, and when it reaches the helicotrema, which is that opening between the scala vestibuli and the scala tympani, and the wave moves all the way back down and pushes out that round window. And this is an illustration of how the traveling wave moves along the length of the basilar membrane, much like how when you are making ripples in a sheet of cloth. But remember, on the basilar membrane, are those hair cells that are sitting on the top over here, on the top of the basilar membrane, so when the top moves, along the length of the cochlea, they displace the hair cells that are sitting on the top of the basilar membrane. Just a reminder again, in the powerpoint version of this lecture, all of these hyperlinks should work and I encourage you guys to visit these websites to supplement the information that we are talking about in this lecture. So again, since the whole inner ear in kind of embedded within the bone of the temporal bone, any pressure created by this oval window displacement has to be dissipated, and that is the role of the round window at the bottom, over here. So whenever the oval window is depressed inside, the round window actually pops out to displace this pressure. And depending upon the frequency of the sound that is conducted within the inner ear, different areas of the basilar membrane are stimulated, and that depends upon the physical properties of the basilar membrane. So in this illustration, you are seeing the stapes and basilar membrane like a long sheet of cloth, above that, you are seeing the hair cells, so we’ve got the outer hair cells, which are far many, arranged in 3 to 5 rows, while we’ve got a single row of the inner hair cells over here. So the frequency determines where there’s a maximum displacement of the basilar membrane. And this hierarchical arrangement of frequencies is what we call as tonotopicity, and that seems to be kind of an underlying theme all along the auditory system, that there are different parts within any given structure that responds to some frequencies. So in a way, the basilar membrane acts as a spectrum analyzer, much like a Fourier transformer, kind of teasing out the frequency information from the sound. So here, you’re seeing the displacement of the basilar membrane, again, the hair cells are sitting on the top of the basilar membrane, so they are going to be stimulated depending upon what the frequency of the sound is. The basilar membrane is such that it is narrower and stiffer at the base, the basal end, which is close to the oval window, and it gets wider and less stiff as you go to the apex, so if you were to unwind the cochlea and spread it out like that, you would see that the basilar membrane is narrower at the base and it gets wider as you go to the apex. And that’s what responsible for it to be sensitive to different frequencies. We know from out lectures on acoustic, objects that are stiff and short respond better to higher frequencies, while objects that are long and less stiff respond best to lower frequencies. So if you were to give a sound that is a higher frequency, it results in stimulating the basal part of the basilar membrane, while a lower frequency travels all the way to the apex, and it results in displacing the apical part of the basilar membrane more. Again, this arrangement is what we call as a tonotopicity, so any frequency that falls between this high frequency, low frequency will stimulate, systematically, different areas of the basilar membrane. So here is another illustration of the tonotopicity of the basilar membrane. So we know that the human auditory system can respond to frequencies between 20 and 20,000 Hz. So it’s schematically the highest frequency, 20 kHz, would be the most basal tip of the basilar membrane, while the lowest frequency that we can respond to, namely 20 Hz, would be the most apical tip of the basilar membrane. And you can see in this illustration, the cross section of the different compartments of the cochlea, you can see that the basilar membrane, at its base is narrow, but it gets much wider as you go to the apex. So here’s an illustration showing you how mass and stiffness of the basilar membrane determines the tonotopicity of the basilar membrane. At the base, the mass is low, but the stiffness is high, so that makes it most responsive to higher frequencies, but as you go towards the apex, the mass increases, and the stiffness decreases, making it more responsive to lower frequencies, or low pitch sounds. So here is an animation showing you the basilar membrane as you go from the base to the apex. So if you have a sound that is 2000 Hz, or 2 kHz, it results in this traveling wave having a higher peak closer to the apex in comparison to a 6 kHz or a 6000 Hz, where the traveling wave peaks more towards the base. So hair cells are small, they are in the dimensions of micrometers. But what’s more interesting are those small hair follicles that sit on the top of those hair cells, namely the stereocilia. The stereocilia are of the dimensions of nanometers or 10 to the power of -9 meters. And recently, with all the technological advances, we’ve come up with small tools that actually help us better understand what’s going on in the cochlea, they found that this stereocilia have mechanical gates at their tips. So this is an example of a hair cell and at the top you are are seeing the stereocilia, at the top of the stereocilia are those mechanical gates that are sensitive to displacement. So when they are displaced, they actually result in opening these gates, letting some ions enter into the hair cells, and when they do so, it results in changing the electrical potentials within the hair cells, which ultimately stimulate the auditory nerves, which are connected to the base of the hair cell. And remember just to recollect, these hair cells and the stereocilia lie within a compartment that is filled with endolymph, and one of the important chemical compisitons of this endolymph is that it has a lot more potassium ions, or K ions. These potassium ions will play an important role in the cochlear physiology, but just to recollect that point at this juncture. So again, we are looking at the basilar membrane, above which sits the Organ of Corti. This is a schematic illustration of the inner hair cell, and I know that it is an inner hair cell because it is vase-shaped, unlike the outer hair cells, which are more like test-tube shaped. So the stereocilia sit on the top of the hair cells and surrounded by the endolymph, which has a lot more potassium ions. At the base of the hair cells are those auditory nerve fibers, so, ultimately, the overal role of the auditory system is to convert the mechanical, acoustical sound waves into a form that the nervous system can understand, so the inner hair cells role is to actually convert those mechanical movements into an electrical form that will be carried by those auditory nerve fibers towards the brain. So in relation to the hair cells, there are two important membranes: one we talked about the basilar membrane at the bottom, and hover at the top is this tectorial membrane. The way they are placed within this scala media is such that they have two different pivotal points. So when the basilar membrane is being displaced by the traveling wave, up and down, this results in what we call as a shearing action in these two membranes. So in this illustration, you can see that when the basilar membrane is being displaced upwards, it results in this shearing action that kind of tilts or pushes the stereocilia in one direction and the opposite happens in the negative phase of the traveling wave, when the basilar membrane is displaced downwards; the stereocilia are moved in an opposite direction. So when the stereocilia are being displaced, that is when those gates, on the top of the stereocilia, are opened. So when they open, the potassium Ions, those K+ ions, and I am sorry they are really small in the picture, enter into the cell and result in changing the electrical potential within the hair cell. Something we call as depolarization. So when this depolarization happens, it results in a positive current that stimulates the hearing nerve fibers that are attached to the base of the hair cells. So you can see that the shearing force acts because of the two different pivotal axes for the tectorial membrane and basilar membrane, kind of tilting the stereocilia in one direction when the basilar membrane is moved up and in the opposite direction when the basilar membrane is moved down. Again, another anatomical significant point, is that the tectorial membrane is in direct contact with the stereocilia of the outer hair cells However, the stereocilia of the inner hair cells are close to the tectorial membrane, but they are not in direct contact with the tectorial membrane. So when the traveling wave results in this relative displacement of the basilar membrane, the stereocilia of the outer hair cells are the ones that are deflected, directly. However, when the stereocilia of the outer hair cells are deflected, they end up pushing fluid that is locked between the tectorial membrane and the Organ of Corti towards the inner hair cells. So it’s this fluid movement that actually stimulates the stereocilia of the inner hair cells, and that is believed to have a protective function. So when there is a loud sound, or a large displacement of the basilar membrane, because of the loud sound, the stereocilia of the outer hair cells are the ones that are actually going to get the brunt of that deflection. In pathological cases of acoustical trauma, for instance, Veterans exposed to loud blasts, if you were to look at the pathology or their Organ of Corti, you would see that it’s actually the outer hair cells that are affected. In some extreme cases, the outer hair cell stereocilia are actually kind of pulled out and they’re lost. While the inner hair cell stereocilia do not get the brunt of this trauma, so they are protected, in some means, by these loud sounds. And why? Because the inner hair cells, we know, receive the majority of the afferent or sensory innervation, so they play a direct role in stimulating those hearing nerves. So it’s important, and we have few inner hair cells than that of outer hair cells, so it’s important to kind of preserve them, so this indirect contact with the tectorial membrane sort of favors this. So, again, recent research has suggested that the inner hair cell stereocilia are moved by the force of the fluid that are being displaced by the outer hair cell stereocilia. And not by the direct shearing action of the tectorial and basilar membrane. This illustration shows you that it’s the fluid flow from the outer hair cell area towards the inner hair cells that stimulate the inner hair cell stereocilia. So again, those hair cells are responsible for converting the mechanical movement into electrical form that the auditory nervous system/nerve can understand. And this process is what we call as cochlear transduction; transduction in general refers to the physical process of converting one form of energy into another so in this case, we are converting acoustical energy ultimately into electrical energy. This illustration, again, you are seeing the tips of those stereocilia, which has those gates, so when the stereocilia are deflected in one direction, those gates are opened, letting those potassium ions, which are enriched in the endolymph, enter into the hair cell, and when that happens, it results in stimulate the auditory nerve fibers, which are at the base of the hair cell. This change in the electrical potential of the hair cell is what we call as depolarization. In this animation, you can see that deflection results in those gates opening and potassium ions running into the hair cell. This current that is produced because of the stereocilia displacement is what’s conducted by the auditory-vestibular nerve, or the 8th cranial nerve, towards structures in the brainstem, and ultimately it reaches the temporal lobe, where the auditory cortex is located for the final interpretation of the sound. This process, where this electrical energy is conducted through the brainstem to the temporal lobe, is what we call as the central auditory pathway. So the stereocilia deflections are direction sensitive, so if the movement is in one direction, it results in a positive current, while if they are being deflected in the opposite direction, it actually results in a negative current. Many of these pictures are actually animation, so I urge you guys to click on them in the powerpoint, and that’s going to activate that so you can see what’s happening within the hair cells. So again, here you’re seeing a hair cell, on top of which are the stereocilia and when they are deflected in one direction, it results in a positive current, as shown by here, and that’s what we call as depolarization, while the stereocilia deflected in the opposite direction result in a negative current, what we call as hyperpolarization. So when depolarization happens, it results in increasing the firing rate of the auditory nerve, while hyperpolarization result in decreasing/reducing the neural firing, and it’s this code that is conducted to the brainstem structures and the auditory cortex. Another illustration of the depolarizaton and hyperpolarization. You are seeing that deflection in one direction results in excitation and a poistive current in the depolarized state, while the deflection in the opposite direction results in hyperpolarization or a decrease in the firing rate, over here. Again, there are some hyperlinks over here that explain this process and help you supplement the information we just talked about. So, when the inner ear hair cells are being stimulated, it results in electrical fluctuations, so it makes sense that there is change within the electricity of the inner ear, and if you have a sensitive equipment, we actually can record the changes of current within the inner ear. This process is what we call as electrocochleography, where we can record the cochlear potentials, provided we have a sensitive needle that we can get as close as possible to the generators of the potentials. So, electrocochleography in its traditional sense is an invasive procedure, in the earlier days, they actually had a needle pierced through the tympanic membrane with the intention of getting the needle as close as possible to the cochlea. Now a days, we actually have something that looks like tips, covered by gold filaments, that can be left inside the ear canal, and with technological advances, we don’t have to actually pierce the eardrum; we can record this electrocochleo-potential right from the ear canal. There’s four important potentials that are generated within the cochlea. What’s important is that each of those potentials originate from different structures within the inner ear. So, indirectly assessing them will give up information on how healthy these structures are. The first potential is this endocohlear potential, EP, it’s the resting potential within the scala media within the endolymphatic space. It’s a positive potential, and averages about +80 mV, so it’s a really small voltage, but, nevertheless, if we have sensitive equipment, we will be able to measure it. Millivolts, again is a 1000th of a volt, just to give you perspective, the AAA batteries that we typically use are 1.5 volts and you can imagine that you don’t get electrocuted by holding a AAA battery, and we are talking about a 1000th of that voltage, so we are talking about really minuscule changes in voltage. It’s a DC voltage, or what we call as a direct current, and the main structure responsible for maintaining this EP is the stria vascularis, which refers to those blood capillaries that are found in the lining of the scala media, and they’re the ones that are responsible for producing the endolymph and maintaining this EP. The second important potential that originates from the cochlea, is this cochlear microphonic. The cochlear microphonic is an alternating current, much like the current from the sockets in your home where it fluctuates over time; the voltage fluctuates over time. The cochlear microphonic, as the name goes, it’s like a microphone; it picks up sound and converts it into a fluctuating potential. The cochlear microphonic also fluctuates depending on the sound. Now, the cochlear microphonic is produced by the outer hair cells, so if you were to measure cochlear microphonics, and if they looked normal , that indirectly tells us that the outer hair cells are functioning normally. The third potential is the summating potential. The summating potential, like the EP, is a DC current, and it’s a reflection of the inner hair cells, so, again, if we were to record summating potential, that will indirectly tell us how the inner hair cells are functioning. The fourth potential is what we call as an action potential. Action potentials are caused by the auditory nerve firings; it’s a class of responses that we call as “all or none” which is kind of the main way the nerve fibers respond, but, nevertheless, those action potential, if you were to record them using electrocochleography, we will get information on those auditory nerve fibers. So here’s an illustration of those different potentials we were talking about. Those different potentials originate from different structures within the cochlea, and they’re by giving us objective information about how well these structures are working. So here’s a scanning electron microscope picture of the Organ of Corti. We’ve got the stria vascularis, that lining of the scala media, and that’s what is responsible for generating those endolymphatic potentials. The cochlear microphonics is an AC type of electrical potential, and that’s a reflection of the outer hair cell’s activity. The action potentials are neural firing spikes that are a reflection of how well the auditory nerve fibers are working. The summating potential is made possible by the inner hair cells, so assessing the summating potentials will give us information on how well the inner hair cells are functioning. So when we talked about the anatomy of the inner ear, we talked about how anatomists did not understand why we had so many outer hair cells, and why those outer hair cells receive less of the afferent or sensory innervation, while the inner hair cells seem to play a more important role when we have so few of them. Another thing that has baffled anatomists early on was when they were looking at cadaver, they could see the traveling wave, but the traveling wave is what we call as a passive traveling wave in this cadaver or dead ear. This traveling wave kind of had those peaks that was higher at the apex for lower frequency sounds and higher at the basal end for high frequency sounds, but the overal height and the shape of this passive traveling wave was what we call as shallow. In other words, a large portion of the basilar membrane was stimulated for any given sound, and that did not play well with what we are seeing in an active, normal ear. A normal hearing ear seems to be sensitive to very soft sounds, more importantly it’s very sensitive to frequency differences between sounds. So if we were to theorize that frequency is being distributed along the length of the basilar membrane, these broad peaks would not explain how well we can discriminate frequencies. One thing that an earlier examiner observed was that if you were to deprive the inner ear from oxygen, it actually resulted in the broad-peaked basilar membrane movements like what we would see in a cadaver ear. So it seems like oxygen is important for a healthy ear and important for making this traveling wave tall and sharp-peaked. So in the top animation, you are seeing the traveling wave in a passive system, or a dead system, while the bottom is the traveling wave you are observing in an active system, so here you can see the difference between an active system, not only is the height of the traveling wave taller, but it’s also sharp or narrower, now this would explain the high frequency discrimaintion ability that we have. So this lead this earlier examiner, Gold, to believe that there is something active going on in the inner ear that is supplying energy to make this traveling wave taller and sharper-peaked. Only recently, back in the late 70s, David Kemp, who was a researcher at Oxford University, suggested that there is something active going on in the basilar membrane and he provided evidence for that by recording sounds in the ear canal that are actually produced by the inner ear. Historically, we though the inner ear was a passive system, just taking sound, converting it into a form that the hearing nerve can understand; it was not considered to be an active system that is able to generate sounds, but when David Kemp, recorded the otoacoustic emissions, those echos from the ear canal, that provided evidence that supported that something active is going on in the inner ear that is actually producing sound. So all of you guys would observe that if you have an active system, like an active microphone, computer, or anything that is active, a by-product of that activity would be noise, probably when you are listening to this lecture, you’re probably hearing the noise of the laptop or if you were to put your ears to the TV or any active system, you would see that there is some noise going on because of the activity inside. Such is the case for the inner ear; in an active system, you’re having a byproduct of noise, and that’s what we call as those otoacoustic emissions. So, now our understanding of those outer hair cells is that it helps to sharpen the displacement patterns of the basilar membrane, it improves our sensitivity to sound, and that is what is responsible for reducing a threshold, enabling us to listen to very soft sounds. It was exciting to find out that the outer hair cells accomplish this by what we call as electromotility. Mammalian outer hair cells seem to be able to change their length when they are electrically stimulated. So they not only passively take sound, but when they are responding to sound, the length of those outer hair cells actually changes. So such that during the hyperpolarization state of stimulation, the outer hair cells actually elongate, and the depolarization state, or the negative phase of the displacement of the basilar membrane, the outer hair cells actually sharpen or shrink in length. That’s what we call as electromotility. So here, you’re actually seeing one outer hair cell, lying on a petri dish, that is being stimulated, mildly, by a current and you can see that this outer hair cell is actually elongating and shrinking. So when it’s being stimulated by electricity, it actually results in increasing its length, and that’s what is happening in a live or healthy system, so it results in actually pushing the basilar membrane kind of in-phase with the traveling wave, so that’s what supplements this extra energy, making this traveling wave taller and more sharp. So initially, the outer hair cell’s electromotility is because of the fluctuations of the endocochlear potential, because of this passive traveling wave, but once that kicks in, the outer hair cells elongate and shrink, and amplifies this traveling wave, and this is what we call as cochlear amplification. So the outer hair cell’s movement results in a positive feedback that increases the movement of the basilar membrane, thereby reducing the threshold of our sound, enabling us to hear low-level sounds. Also, importantly, it improves the frequency discrimination because these peaks are sharper now, so specific parts of the basilar membrane are stimulated, depending on the frequency, enabling us to discriminate these frequencies. So in this feedback system, we are seeing that the acoustical energy actually results in the basilar membrane displacement. When the basilar membrane is being displaced, it stimulated the stereocilia of the outer hair cells because of the shearing action of the tectorial membrane and the basilar membrane. When that happens, it stimulates the outer hair cells, making it electromotile, in other words, changing its length, longer and shorter, and that actually feeds-in energy, making this traveling wave more taller and sharper. And it’s that improved energy that actually stimulates the inner hair cells, which stimulates the auditory nerve fibers at the base. So now, you can see the role of the outer hair cells serving as a positive feedback energy feeding system, which improves the sensitivity of the inner hair cells to sounds. So the outer hair cells amplify the mechanical input to the inner hair cells, but it’s the inner hair cell that actually carries the information towards the brain. So the outer hair cells are the source for these echos that we can record in the ear canal. And these echos are what we call as otoacoustic emissions; ‘oto’ referring to the ear, acoustic sound emissions. So these are actually very soft sound and if you have a sensitive microphone, and if you were to place that microphone as close as possible to the eardrum, you can actually record these sounds coming out from the inner ear, actually. Actually, these are generated by the outer hair cell, so if you record those otoacoustic emissions, it provides us an objective way of assessing those outer hair cells. Again, outer hair cells are the ones very sensitive to damage, let’s say from excessive noise or because of some drugs resulting in a kind of hearing loss we call as ototoxicity, so usually it’s outer hair cells that are affected first, and, in this case, we are seeing that these otoacoustic emissions are the reflection of the outer hair cells, so now we have an objective way of assessing how well the outer hair cells are functioning. The otoacoustic emissions are measured with a system kind of similar to what we see in tympanometers, so it looks like a probe that is properly fit with a tip, depending upon the size of the ear canal, but in this case, it’s has a sensitive microphone that picks up sounds emitting from the inner ear. Otoacoustic emission testing has become kind of routine test, especially for infants, and it’s, in fact, used in many neonatal hearing screening programs, where they’re using those otoacoustic emission testing to objectively test a person’s hearing. So the outer hair cells are the ones that are very sensitive to damage, from let’s say noise, so in this slide, we are seeing how it’s supposed to look; the stereocilia of the outer hair cells and inner hair cells are supposed to look like that, but when there has been excessive noise, like in noise-induced hearing loss, you can actually see the outer hair cell stereocilia being affected. In some cases, they’re actually lost. For just transient noise exposure, the stereocilia might be kind of deflected or disarranged, but if there is prolonged and excessive noise exposure, you might actually lose the stereocilia cells. Now, again, otoacoustic emissions are a reflection of those outer hair cells, and so you would expect that if there is a noise induced hearing loss, they would have reduced or absent otoacoustic emissions. Another point that we talked about in the anatomy of the inner ear is why is this cochlea spiral shaped? For a long time, anatomists thought that it was just to serve/save space and also as a protective function because now it’s a very small, curved structure so it’s less prone to damage, but recently, just a few years back, some investigators believe that it actually serves another purpose. They believe that the shape of the cochlea helps in boosting our sensitivity to lower frequencies and helps in stimulating the outer hair cells better. An analogy that I think might help in understanding that is waterslides; so all of you guys would have had the experience of going through a waterslide. So you might have a straight waterslide like this or a serpentine, spirally waterslide like that. So when you’re traveling down the waterslides, in the straight slide, you probably can imagine yourself being in the center of the slide all the way down, but if you’re traveling through a serpentine waterslide, you probably would notice that because of the centrifugal force, you’re actually traveling towards the outer periphery; you are kind of angled inside the waterslide when you are traveling down, and more the centrifugal force, the more narrow the curve is. So such is the case of the fluid displacement within the cohclea because of the traveling wave. So the fluid is being displaced along the length of the cochlea, and because of the spiral nature of the cochlea, the fluid movement results in stimulating the periphery of the cochlear duct more and, remember, it’s in the periphery or lateral edges of the cochlear duct is where the outer hair cells are, and you can see that as the spirals become more closer, more the energy or more the force towards the periphery. So that’s what makes us sensitive more to lower frequency sounds because that fluid movement is more forceful at this apical end, at this narrower spiral end. I thought that that was interesting and pretty cool theory. Just to summarize, acoustical energy of the sound wave is converted into mechanical energy by the tympanic membrane, this mechanical energy is conducted by the ossicles in the middle ear, and ultimately resulting pushing the footplate of the stapes in and out in the oval window, so that results in fluid movement, In other words, hydraulic energy, this fluid movement results in the deflection of stereocilia of the inner hair cells, and it’s this deflection of the stereocilia that results in the electrical energy at the base of the hair cells, which is conducted by the auditory nerve fibers towards the brainstem and the cortex, and in the temporal lobe, those electrical impulses are interpreted as sound. So here’s a synopsis of what is happening in the whole auditory system, where the acoustical energy is converted into mechanical energy in the middle ear, and then it’s ultimately converted into electrical energy in the inner ear. The same thing in the form of a flow chart. Where sound energy is ultimately converted into electrochemical energy.