Neuroanatomy: 8:00 - 9:00 Scribe: David Davis

Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 1 of 7 I. The Vestibular System [S1] a. I am going to cover vestibular systems first, then I will talk about eye movements. Those two sort of form a grouping. Then, we will switch gears and talk about motor systems, specifically motor unit recruitment, spinal reflexes and the like. II. Picture of inside the ear [S2] a. I am going to try and hit only the high points of these lectures. I want you to know what I tell you. I will try and organize it in a way that you can actually not get overloaded with information. b. Why don’t we fall in the dark? c. First, a little bit of an overview of the anatomy of the vestibular system. You have heard about the cochlear and you have heard about the auditory system. You know you a little bit about hair cell physiology. I will tell you a little bit about the semicircular canals, which are part of the vestibular system, as well as…let’s just focus here, here are the semicircular canals. III. The Vestibular Organs Sense Head Motion [S3] a. This shows us a better view of the semicircular canals and in addition to the other components of the vestibular system, the otoliths, which are the sacculus and the utricle. b. The major components of the vestibular system are the semicircular canals, which sense head rotations and I will explain that in more detail in a minute. c. The otolith organs, the sacculus and the utricle, sense linear accelerations. By linear accelerations, the most important linear acceleration you experience in day-to-day life is gravity, which is accelerating you right now towards the center of the earth at 9.8 meters per second squared. d. Gravity is an acceleration. You aren’t actually moving, but it is accelerating you. e. Other accelerations, linear accelerations, would be those that you experience when you accelerate from a traffic light in your high performance sports car. If you stop suddenly, you experience linear acceleration. IV. The function of the vestibular system….[S4] a. Rotations of the head occur with basically shaking the head this way and this way and nodding. This occurs with regular movements of the body. These can be planned or unplanned movements. b. Basically, between the semicircular canals and the otoliths, you can sense both rotations and linear accelerations. c. People have come up with a terminology to describe rotations of the head. They are based on nautical background. You may come across these three terms for head rotations that you should be familiar with. d. There is roll, which is this rotation of the head – around the nose. e. There is pitch as in your head going up and down like this. f. There is yaw where your head is going like this. g. So, you have yaw, pitch, and roll. h. Not complicated but you should be familiar with what they are talking about.

V. Vestibular outputs very rapidly influence eye, head, and postural reflexes [S5] a. The vestibular system is important for three major functions. b. Those that are interested in eye movements; it underlies the vestibulo-ocular reflex, which is reflexive movement of the eyes to compensate for head rotations. For example, if you hold your finger out in front of your head like this. Look at your finger. This is an actual clinical test. While looking at that finger, shake your head back and forth as quickly as you can and then tell me how fast you can do it. i. If you have normal vestibular function, you should be able to shake your head really fast and still be able to fix your finger. c. In contrast, if you move your finger at that rate, there is no way that you can track it. If you just move your finger, you can’t. d. The vestibular system is really quick. It accurately compensates for head movement and it allows you to maintain fixation despite head movements. It works in not only the horizontal but you can do this and this. e. Anyone with vestibular damage, as soon as they do this test they will say that the finger is blurry. You all could do that, but any vestibular deficits, you can’t do that. f. That is an important test and it is an easy one to do. g. Vestibulo-colic is a reflex. It is a neck muscle. It is where the head position is maintained despite body movements. For example, if I wanted to keep my head upright, I should be able to do that. Despite your head going backwards and forwards, you should be able to keep your head relatively level. h. It isn’t quite as fast as the vestibulo-ocular reflex but it is still pretty fast. i. Finally, vestibulospinal, which you learned about or should have learned about, you know about the projections and we will talk about those. These are the postural changes that are acquired in the response to vestibular signals to maintain balance if you go this way or this way. You will notice that I am actually not falling over. Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 2 of 7 j. Obviously, if one consumes too much alcohol, some of these vestibular reflexes don’t perform as well. We aren’t going to do that as a demonstration.

VI. Scanning electron micrograph of hair cells from the bullfrog inner ear [S6] a. The underlying sensory component of the vestibular system is the hair cell. The hair cell is present in the semicircular canals and in the otolith organs. It has a classical hair cell like organization, which involves a number of little, what are called, stereocilia. We have talked about these briefly in the sensory transduction lecture. b. This is an unusually kind of cilium in the bullfrog inner ear. c. These are actually bundles of stereocilia. They have one orientation because the kind of cilium is located at one point in this bundle. d. That is what we are talking about when we talk about a hair cell and its stereocilia and kinocilia.

VII. Figure 25 [S7] a. Then, we usually show pictures, which show a cross section through a hair cell. Remember, a hair cell is the sensory cell. It does not directly project to the brain. Instead, it has stereocilia and kinocilia. i. Movement of the stereocilia away from or towards the kinocilia affects the membrane potential of the hair cell that affects neurotransmitter release. That, in turn, affects the postsynaptic cell. That is what relays information to the brain in the 8th nerve. b. So, hair cell physiology. How do hair cells detect movement of the stereocilia? c. We talked briefly about this. Stereocilia are connected with these little tip links d. VIII. Picture of a Hair Cell [S8] a. We talked briefly about this. Stereocilia are connected with these little tip links and there are mechano-sensitive channels right here at each of the stereocilia. b. When the stereocilia move toward the kinocilium, the tip links get stretched and the mechanoreceptive channels can open up. I am going to show you a diagram now, which basically summarizes these conditions.

IX. The mechanisms underlying the depolarization…..[S9] a. This actually takes you from the movement of the stereocilia all the way to the firing rate of the vestibular afferents, which signal movement of the stereocilia. It is showing three conditions. i. The first condition is the resting condition in a vestibular hair cell and vestibular afferent. This makes a number of points so we are going to spend a little time on it. 1. At rest, there is a steady influx of potassium into the stereocilia at the tip links. A little steady influx of potassium causes the cell to be somewhat depolarized form resting. At rest, it is slightly depolarized. What this diagram shows is a steady release neurotransmitter, which is aspartate and glutamate from the hair cell onto the postsynaptic side of the vestibular afferent and that results in a sort of moderate opening of channels. These are nonspecific cations in the postsynaptic membrane and hence the postsynaptic membrane is somewhat depolarized therefore has a resting firing rate of, in this case, somewhere in the range of 90 action potentials per second. This resting rate may very be as low as 50, or it could be a little higher. The main thing is that there is a resting rate in vestibular afferents. They are firing maybe 90-100 spikes per second, which is a relatively high rate of firing at rest. The reason that this is important is that means that they can both increase their firing rate with stimulation in one direction, but they can also decrease their firing rate. They can signal with both decreases of their firing rate and increases in firing rate. They can be sensitive to motion of the stereocilia in both directions. ii. Let’s assume that in fact that the stereocilia are deflected so that the kinocilium are moved in this direction so that the channels, basically the tip links are now opened more, the mechanosensitive channels are opened more and they will be a greater influx of potassium, which depolarizes the cell more and under those conditions, greater depolarization of the hair cell will cause greater release of the neurotransmitter, which is what I said – aspartate and glutamate. Greater release of neurotransmitter will cause greater opening of the postsynaptic channels and cause this membrane to be more depolarized, which will be, in this case, -30 in the hair cell and the postsynaptic side. More depolarization of the vestibular afferent will raise it above the spike threshold and it will cause it to fire increased action potentials. The vestibular afferents respond to stereocilia movement towards the kinocilium. The net result is vestibular afferent discharge rate that increases. That situation there leads to this. iii. In contrast, if the stereocilium move away from the kinocilium, then the stretching of the tip links is decreased, the potassium channels close, there is no influx of potassium. The hair cell hyperpolarizes. The net result of that is there is a decrease calcium influx, decreased neurotransmitter release, and the net Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 3 of 7 result is that the postsynaptic membrane hyperpolarizes and therefore, the vestibular afferent discharge rate decreases. iv. Bottom line is when stereocilium move away form the kinocilium, as shown here, the net result is the vestibular afferent discharge rate decreases. v. Just remember that one. Just visualize the stereocilium moving away from the kinocilium and a decrease in vestibular afferent discharge rate and the converse is true. vi. Then, remember that at rest, there is a spontaneous firing rate in the range of 90-100 spikes per second. vii. Those are the take home messages and this is true for all vestibular hair cells, but how these stereocilium moves in response to head movements varies between the semicircular canals and the otolith organs. I will talk about that. X. Linear Acceleration [S10] a. Let’s first consider linear acceleration, which is signaled by the otolith organs. So, the importance of these are – what you should know about this is a hair cell bundle, as I showed you from the bullfrog, and each bundle is polarized in the sense that there is only one kind of cilium and that is that one extra large black dot here. This hair cell bundle is going to be sensitive, it will depolarize when the stereocilium move in this direction, which is the direction of the arrows. This means that the vestibular afferents will increase their firing rate when there is a net movement in this direction and they will decrease their firing rate when their movement is against the arrow. b. The two major players in the otolith system are the sacculus and the utricle. Within the sacculus and the utricle, there are usually two subdivisions and the sensitivity to linear acceleration is shown by the arrow direction here. c. For example, here is the sacculus and in this part of the sacculus, here, the posterior part, this part is sensitive to linear accelerations in the superior direction and this part is sensitive to linear accelerations in the inferior direction. d. Then, as you move up to this part of the sacculus, here you can see that the bundles of hair cells are sensitive to linear accelerations posteriorly and anteriorly. e. You have posterior and anterior covered and inferior and superior covered. That is within the sacculus. f. The utricle is organized differently in the sense that it has a medial and lateral component. It is organized like this. There, if you look at the sensitivity of the utricle, you can see in this part, which is the anterior part of this horizontal structure, it is sensitive to linear accelerations laterally and linear accelerations medially in this part. g. Between these two structures, they are sensitive to linear accelerations superiorly, inferiorly, anteriorly, posteriorly, medially, and laterally, with some overlap. h. They cover all of the potential axes of linear acceleration. i. The sacculus and utricle – different hair cells are tuned to different linear acceleration directions. j. In addition, in the semicircular canals, all of the hair cells are tuned to linear accelerations – tuned to fluids within the semicircular canals. k. In the ampulla, which is the fluid in the semicircular canal, the hair cells are tuned to only one direction of sensitivity. We are going to talk about the semicircular canals in just a minute. In the ampulla, all of the hair cells are polarized in one direction. l. The utricle and the sacculus have this directional tuning.

XI. Scanning electron micrograph of calcium carbonate crystals, Figures 14.4 and 14.5 [Slides 11-13] a. The other thing to note is that the sacculus and the utricle contain hair cell bundles, stereocilia and kinocilia, which are sensitive to linear acceleration. b. These stereocilia and kinocilia are sitting out there and in order to make them more sensitive to linear acceleration, basically what happens is that there is a jell-o like, it isn’t jell-o, a gel like substance that the stereocilia are embedded in – this is for the utricle and the sacculus. c. Within this gel-like substance, there are, what are called, otoconia, which are very small calcium carbonate rocks. d. You do have rocks in your inner ear. Each crystal in humans is about 3-30 microns long. They are relatively small, calcium carbonate crystals and they sit on top here. The otoconia sit on top of this gel like membrane in which the stereocilia and kinocilia are embedded. e. Imagine a bowl of jell-o being jiggled back and forth. Imagine this stereocilia and kinocilia embedded in a gel like substance with small rocks on top, which are sensitive to linear accelerations. This is a mechanical amplification system basically. The gel and the rocks make it very sensitive to linear accelerations. f. Now, the only other issue that is a source of confusion for this utricle and the sacculus – a potential source of confusion – is that, as I said, you are undergoing a constant acceleration, which is gravity. So, there are two ways in which the kinocilium and the stereocilium can be deflected in the utricle and the sacculus. Two ways. i. One way is through static tilt. So, if you just tilt the membrane, like this, because of gravity, the relationship between the stereocilia and the hair cell – there will be a deflection. If I tilt my head like this, gravity is working differentially and specific hair cell stereocilia bundles will be deflected, which means that I can Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 4 of 7 interpret that as a head tilt. If I close my eyes, I can tell that I am tilting my head here. You can always tell that you have a head tilt because gravity is working on the otoconia to cause deflection. So, that is head tilt. Static tilt. ii. The other problem for the vestibular system is that I can also get these hair cells, these stereocilia, to tilt if in fact I don’t tilt my head, but instead I accelerate away from a stop sign in my high performance sports car. My head will be straight up, but the acceleration on the otoconia will cause them to deflect. Even though my head is straight up here, I can get tilting of the stereocilia if I accelerate in different directions. So, there is some ambiguity about the signals. You can get these stereocilia to tilt either because you are actually tilting the head or because you are accelerating back and forth. That is in the frontward domain. There is that ambiguity. iii. A brief acceleration could potentially be interpreted by the brain as a brief head tilt. iv. The vestibular system tends to treat these two signals differently. So, the rule of thumb appears to be, if the signals from the vestibular system are relatively slow and prolonged then the brain tends to think they are head tilts. If they are rapid, which would be consistent with you jumping off of a brick wall or something like that – a quick acceleration – that would tend to be treated by the vestibular system as an acceleration. v. That can cause some confusion. I knew someone that was a former pilot who took off from aircraft carriers where they were accelerated off the decks with those cannons and then they go up and under those circumstances, they get an acceleration that lasts for some time. They go up and apparently, if you trust your vestibular system, you believe that you are actually tilted. The sensation is that you have actually been tilted and apparently the response is that if you trust your vestibular response, you apparently think that you are going nose down into the ocean. Your tendency is to pull up in which case you would stall and crash. Apparently, you have to fly by instruments after you take off. If you trust your vestibular responses, you crash. There are other cases where the vestibular system for low turns, the vestibular system is not that reliable. The vestibular system is designed, or evolved, to deal with normal movements around the world – jumping off tables, climbing things like that. There are ways to fool it. vi. Under most circumstances, it will work well and it will distinguish between head tilts, like this, and brief accelerations. That is the linear acceleration system. vii. It is important, for example, if you are moving sideways. It will compensate appropriately with - I am talking about with ion movements, but it also handles neck movements and body movements. viii. That is the utricle and sacculus – linear acceleration.

XII. Figure 14.6 [S14] a. Another thing to note - As I said, it detects – afferents have a resting rate. Here, the resting rate of this afferent is 40 spikes per second and it will increase with tilt in one direction – so it can signal tilt in one direction by increasing firing rate of the vestibular afferents – but, importantly, it will also signal tilt in the other direction by decreasing firing rate, not quite as much, but it still signals both directions, which is one of the reasons that if you have damage to the vestibular system unilaterally that it is potentially possible to use just a unilateral vestibular system to recover some function. It does take a quite a bit of rehab. b. The other thing to note is that this is a sustained tilt and the firing of the cell is maintained for the, well almost a minute and a half of tilt, so the otolith organs do not adapt during sustained tilt. I can stand here with my neck like this for minutes and I will not adapt. As we will see, the semicircular canals do show adaptation to constant velocities. The otolith system does not adapt.

XIII. Figure 14.7 [S15] a. Let’s switch these and talk about the angular acceleration. How do we detect angular acceleration? Instead of jumping off desks, landing with a linear acceleration or accelerating away, now we want to basically deal with head nodding, rotations, and things such as pitch, roll, and yaw. b. There are three semicircular canals on each side. We are going to talk about their organization in a moment. Each one is fluid filled and the basic principle of operation is that if the rotation is along the axis or in the axis of a semicircular canal, fluid as you tilt and rotate around the semicircular canal, fluid will move in it. As the fluid moves in the semicircular canal, it acts on this structure, which is contained within the ampullas. So, there is a specialized swelling at the base of each of the semicircular canals called the ampulla. It contains a membrane, which is rather like a sail. So, just think of this sail catching this fluid in the semicircular canal and as the fluid catches the cupula, it will cause it to deflect. So, this is our sail-like structure sitting there in the ampulla and it is very sensitive to fluid movement in the semicircular canal. When the cupula catches this fluid movement, it acts, as you noticed, it is actually the stereocilia of the hair cells that insert into the cupula and appropriately get deflected. Fluid movement in the semicircular canal act on this sail like structure, again this is an example of mechanical amplification, so, very small changes in fluid movement will cause this bellowing copular to move back and forth, well not really but it causes it to move back and forth (?) and that will cause these stereocilia to Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 5 of 7 move back and forth. That is the specialized structure in the semicircular canal that detects fluid movement in the semicircular canals.

XIV. Figure 14.8 [S16] a. I have a little diagram up here to show you that. So, here is the – this is during no rotation. The cupula is sitting there, the semicircular canal with no fluid movement. Now, assuming that you suddenly rotate in the plane of the semicircular canal. As you move it in this direction, the fluid, which is endolymph, pushes back on the cupula. You guys can think about this if you have ever taken a glass of water and moved it around, you know that if you move a glass of water to the left, the water tends to shoot out of the glass to the right. If you move it too quickly, it spills. So, the endolymph moves that way. The endolymph works on the cupula, it deflects the stereocilia toward the kinocilium and that will cause an increase in the firing rate o the vestibular afferents from this particular ampula. b. That is the basic mechanism. Fluid moving in the semicircular canal pushes on the cupula. The more the motion, the greater the increase in firing rate of the vestibular afferents. If it moves in the other direction, the vestibular afferents decrease their firing rate. They can signal in both directions of rotation. c. There are three pairs of semicircular canals – actually, there is a pair of three of semicircular canals - on the left and on the right hand side. There are the horizontal canals on the left and right hand sides. Although they are called the horizontal canals, they actually are tilted up slightly. Their absolutely preferred orientation is 30 degrees tilted up from the horizontal. Those are most sensitive to horizontal head movements, hence their name. They work as a functional pair. When I say a functional pair, that means if the head movement - if I turn my head to the right, then the signals in the right horizontal canal will be equal and opposite to the signals of the left horizontal canal. They are operated by what is called a push pull system, so when there are increases in the right horizontal canal, there are decreases in the left and vice versa. They work as a functional pair. The other semicircular canals work as functional pairs as well but, it is a little more complicated for that. d. There are both the posterior canals and anterior canals on each side. The pairing of those work out such that the left posterior canal, its preferred direction of rotation matches the right anterior. So, the functional pairing of those are the right anterior, left posterior, hence RALP. An acronym that you can remember, some people prefer RALP and other people prefer LARP. If you know one, you can always work out the other. The pairings are left anterior, right posterior, or right anterior, left posterior. Those are the functional pairings. e. So, for example, if there is an increase in the left anterior as a result of head movement, there will be a decrease in the left posterior. Again, they work as a push-pull pair. f. With that, you are covering rotations in all head directions.

XV. Picture [S17] a. This is another diagram just to make it a little clearer. I think I am just emphasizing here. This also shows the plane of the horizontal canal. b. Just as a reference, I have also shown that the utricle lies in this plane – relatively horizontal, with a 30 degree up – and the saccule is in this plane, just for reference. We have all of the vestibular apparatuses preferred planes shown here. c. Here is the posterior preferred and there is the anterior. So, left posterior, right anterior. The color-coding shows how they are paired. That is just to emphasize the pairings of the semicircular canals. d. I have a question. Just to see if you paid attention. It is important to know this functional pairing. Basically, damage to specific semicircular canals will produce specific signs. e. RALP was the right answer. (Sorry, he didn’t say the question or choices in the audio)

XVI. Figure 33-8 [S18] a. The semicircular canals are sensitive to head rotations and we talked about angular accelerations. Now, we are going to start talking about how the signals from the vestibular system are used to compensate for head or body movements. b. We are going to focus on the horizontal canals because it is easier for us to describe it. Everything now when we talk about the vestibulo-ocular reflex, it will be in the horizontal domain. Remember, there are the other pairs of semicircular canals that act in the other directions, but it is just a lot harder to explain how they work together and you guys don’t need that level of detail. So, we are going to stick in the horizontal. Just remember they are working in the similar fashion for head movements in the vertical and oblique directions. c. Very simply, if we look at the signals coming out of the vestibular system when we do a head motion, a rotation of the head to the left, we can look at the signals to the left and the right horizontal semicircular canals. d. Here is the ampula drawn as a cartoon. Here are the hair cells and these are the signals from the vestibular afferents. So, the net result is if the head turns to the left, then there is a – think about this – if the head turns to the left, which way will the fluid move? The fluid moves in the opposite direction. Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 6 of 7 e. First, remember that if the head turns this way, here is the fluid motion – opposite direction of the head turn. The preferred direction of the hair cells in the left horizontal is this way and the preferred direction of the right is also this way. When the head turns to the left, the fluid goes this way. It causes an increase in firing rate of the vestibular afferents on the left hand side and it is in the nonpreferred direction in the right horizontal canal so it causes a decrease in firing of the vestibular afferents on the right side. f. That is a very simple push-pull system. The head turns to the left, increase in vestibular afferents on the left, decrease on the right. g. XVII. Vestibular nerves signal head velocity [S19] a. Now, here is a slight wrinkle. It isn’t that critical. It is important for the vestibulo-ocular reflex. Although, the semicircular canals are sensitive to angular acceleration, when people have recorded from the vestibular afferents and they have done this extensively in behaving squirrel monkeys, what they find is, in fact the activity of the vestibular afferents more closely follow head velocity than head acceleration. That isn’t a big deal. What it means is that the signals from the vestibular nerves for angular rotations really follow quite closely head velocity. b. So, when the head velocity moves in one direction, say at 30 degrees per second, in the vestibulo-ocular reflex, you will find that the eyes will go in the opposite direction at 30 degrees per second if everything is working. c. There is a mechanical effect of the way that the fluid moves in the semicircular canals. It isn’t critical except when you start talking about ion movements. Generally, they signal head velocity. That is the major signal and that helps us understand how they actually signal ion movements appropriately.

XVIII. Vestibular projections to the spinal cord [S20] a. Let’s just quickly talk about the projections to the spinal cord and some other locations before we move into how these vestibular signals are used for certain ion movement control. b. There are vestibular projections to the spinal cord. Those are involved in postural reflexes. You should be aware that there are both the medial vestibular spinal tract and the lateral vestibular spinal tract. c. If you notice here, there are vestibular afferents to the lateral vestibular nucleus, which gives rise here to the lateral vestibulospinal tract. Here are afferents coming into the medial vestibular nucleus, which project bilaterally to the medial vestibulospinal tract. Notice that this medial pathway terminates bilaterally in what would be considered more postural motor neurons. We will talk about that briefly in a moment. The lateral one goes to the motor neurons that are more involved in the peripheral control of elbow and limb movement. d. I think I have those in a bit more detail on the next slide.

XIX. Lateral Vestibulospinal Tract [S21] a. For those who are interested, this is the lateral vestibulospinal tract. Basically, mainly from the otolith organs and it is powerful excitatory influence like extensor and antigravity muscles. b. This is involved in postural reflexes and in fact, most of the vestibulars are. They are involved in reflexes to maintain position despite movements of the body.

XX. Medial Vestibulospinal Tract [S22] a. The medial vestibulospinal tract – this one regulates head position mainly so it is mainly going into head position involving neck muscles. This would be the vestibulocollic response mainly. It is particularly involved in keeping your head up when you trip forward. It is involved with things like that. b. So, their responses of the motor system in response to vestibular stimulation due to tripping or body movement.

XXI. Vestibular signals are sent to cortex [S23] a. The other thing that you should notice is something you should know. The vestibular system – we always talk about the vestibular system as being controlling reflexive movements of the body or eyes or neck in response to external stimuli, but it also has significant projections to the parietal cortex and part of the somatosensory cortex, which allows me, in theory, if I close my eyes, I should be able to navigate here using vestibular signals. I was basically using my otolith signals to detect linear accelerations. There was no visual feedback. The vestibular signals go into parts of the brain that are involved in keeping track of where you are in your spatial location. You can use vestibular signals relatively reliably in the absence of visual signals. They are not as good, obviously. b. They can be used in cortical areas to let you move around in a dark room that you know that you are moving. Experiments have been done on that. c. One of the things that people should be aware of is that as you get older, the vestibular signals of the hair cells slowly die unfortunately. Older people have less reliable vestibular signals, which is one of the reasons why they tend to be prone to falling down especially when they don’t have lights on. If you have the lights on, you can usually use visual signals to guide you, which is apparently one of the reasons that older people are more prone Neuroanatomy: 8:00 - 9:00 Scribe: David Davis Friday, February 5 Proof: Melissa Precise Dr. Gamlin Vestibular System Page 7 of 7 to falling if the lights aren’t on. That is just a small piece of information. There is a reason why they are more prone to falling.

II. Vestibulo-ocular reflex [S24] a. One of the better-understood aspects of the vestibular system is the vestibulo-ocular reflex. This is a relatively straightforward reflex and we consider it in the horizontal domain. It only involves a few synapses. It is amazing how people can get confused on it sometimes. I don’t know. b. We are going to talk briefly about the vestibulo-ocular reflex and we are going to talk about it a little more in the next hour. I will just give an introduction to what the vestibulo-ocular reflex needs to do in the horizontal domain. c. If your head moves to the left, if I’m looking at my finger and my head moves to the left, my eyes should move in an equal and opposite direction to the right. In order to do that, if I am moving my head to the left, my eyes, both eyes need to move to the right. That means that my lateral rectus of the right eye has to contract. The medial rectus of my left eye has to contract. d. Medial rectus in my right eye has to relax. The lateral rectus of my left eye has to relax. We have four muscles to worry about. Only four, shouldn’t be too complicated. e. Here we are. Lateral rectus, medial rectus, lateral rectus. f. This is a diagram. Assuming this is the right eye, so this diagram assumes that this person is peering out of the screen at you. Don’t get confused. I think this is why some people get confused. This is the right eye, this is the left eye. If we look at this, this is the left hand side. Two of the things that you should know – the lateral rectus motor neurons lie in the abducens nucleus. Are you all familiar with that? That is the 6th nerve nucleus. In the 6th nerve nucleus, about 60% of the cells are motor neurons and send signals from the abducens nucleus to the lateral rectus muscle. In addition, about 40% of the cells of the abducens nucleus are what are called internuclear neurons – abducens internuclear neurons. g. Instead of projecting to the muscle, they relay the signals that come into the abducens nucleus to the contralateral medial rectus motor neurons. Whenever the abducens nucleus gets a signal to move the eyes horizontally, that information is relayed to the medial rectus motor neurons on the other side through this pathway in the medial longitudinal fasciculus (MLF). Again, we will talk about this yoking mechanism, but this is an important pathway. So, whatever the signals are that come into the abducens, they are relayed within about 2 milliseconds or 3 milliseconds to the medial rectus motor neurons on this side. h. If the abducens nucleus on this side, on the right, for example, here, the right – the motor neurons there increase their firing rate. Then, in a very short order of time, the medial rectus motor neurons on this side, which is the left, will also increase their firing rate. You need to know that mechanism. i. Then, you need to know one other thing. If you look at the signals coming into the vestibular system, this is again a horizontal head rotation. So, head rotation to the left will cause an increase of firing from the vestibular afferents coming in here to the vestibular medial nucleus. There are two groups of cells here. j. One group sends excitatory connections to the contralateral abducens nucleus to cause increase in firing and another group sends connections, which are inhibitory to the ipsilateral abducens nucleus, which will cause a decrease in firing. k. The net result is – let’s just see if we can work this through before we take a quick break. l. If there is a head turn to the left, there will be an increase in firing rate in the medial vestibular nucleus. m. Those excitatory connections will cause an increase in firing of the right lateral rectus motor neurons through this pathway. Then, through the internuclear pathway, there will also be an increase in firing rate of the left medial rectus motor neurons. So, we have the right lateral rectus and the left medial rectus contracting. This inhibitory pathway causes a decrease in the abducens motor neurons going to the left eye so there is a relaxation of the left lateral rectus and through the internuclear pathway, there is a relaxation of the right medial rectus. n. So, the net result of that is that when the head turns to the left, the eyes turn to the right. I think all of those muscles went in the right direction. Did they? We will go through this again in the second hour.

III. VOR gain is low at low frequencies [S25] a. We are going to skip this slide. b.

[end 49 min]