Scientists Solve Mystery Of Ear-Splitting Sounds Reporting in Nature, researchers write that a rare type of neuron in the inner ear may process painfully loud sounds, such as the blast of a jackhammer. Study author Paul Fuchs discusses how his team solved a mystery that had stumped auditory scientists for nearly 50 years.

Scientists Solve Mystery Of Ear-Splitting Sounds

Scientists Solve Mystery Of Ear-Splitting Sounds

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Reporting in Nature, researchers write that a rare type of neuron in the inner ear may process painfully loud sounds, such as the blast of a jackhammer. Study author Paul Fuchs discusses how his team solved a mystery that had stumped auditory scientists for nearly 50 years.

JOE PALCA, host:

Now we switch gears to talk about ears.

(Soundbite of laughter)

PALCA: That's a little like the start of a Dr. Seuss poem. In any case, there's something interesting new - there's some interesting new work out this week on hearing. We've all heard stuff so loud that we had to cover our ears, you know, think of a jet engine or a rock show, but how do we know, how does our brain know when our ears have reached a volume or are hearing something that's at the danger level? Well, my next guest and his colleagues have discovered that a small subset of the neurons in the inner ear might be the ones that control that. These neurons themselves aren't new to science. Scientists have known about these for quite a while, but this is a kind of a classic piece of science. These neurons were there, they knew they were there, but they didn't know what they were doing there. And now they might have the answer, and the research appears in the journal Nature this week.

Joining me to talk about it is Paul Fuchs. He's co-director of the Center for Sensory Biology at Johns Hopkins University in Baltimore. He's also the John Bordley Professor and Director of Otolaryngology, that's ear nose and throat, research there. Welcome back to SCIENCE FRIDAY, Dr. Fuchs.

Mr. PAUL FUCHS Co-director, Center for Sensory Biology, Johns Hopkins University): Hi, thanks a lot for having me on the show.

PALCA: Well, you're welcome. So I think - oh, and we'd like to ask listeners, as well, to come along and talk about this, if you can hear us out there, 800-989-8255. And I think the first thing we should talk about is that - how does - and then we have to a little primer about how sound gets into the air and then gets to the brain and how the brain makes sense of that. That, you know, that should only take a few minutes, 200 years of research.

Mr. FUCHS: Thirty seconds, I'm sure, is more than enough. Okay, so here we go. The sound waves in the air set the eardrum into motion. That's a pretty familiar topic to any of us. And that's coupled into the inner ear through the middle-ear ossicles. So there's three little bones in the middle ear that couple the movements of the eardrum into the fluids that fill the inner ear itself, which is called the cochlea.

So now you've got sound waves in the air that have become fluid motions in the inner ear. And that then, in turn, sets into motion little mechano-sensory cells called hair cells because they have a little bundle of microvilli that look like hairs. When those hairs get bent by the fluid motion, that changes the electrical properties of that cell.

So that's transduction. That means it's converted sound waves, mechanical energy, into an electrical signal in this little neuro-epithelial cell called a hair cell. So that's the first step.

Now that's good because the brain works with bioelectricity. So we've got a little electrical signal in the hair cell, but the hair cell's a tiny little cell. It's only maybe 10 microns, 10 millionths of a meter in length, and it doesn't reach to the brain itself. Instead, it communicates with a nerve cell that has a long axon and carries information to the brain. And the sensory hair cell communicates to that nerve cell by releasing an excitatory neurochemical called glutamate. So once the hair cell's membrane potential, once its electrical signal is generated, then it releases this glutamate, which excites the afferent neuron, the neuron that goes to the brain, and that carries the actual signal to the central nervous system.

PALCA: Right. Okay, now just because I've been writing furiously, I'm going to go over that one more time to make sure I've got it.

Mr. FUCHS: Okay.

PALCA: Sound waves come in the outer ear. They make the outer eardrum vibrate. That gets transmitted through the middle ear to these three small bones into the inner ear, where it sets up waves of this fluid that's in the inner ear. And inside the inner ear, there are these little hair cells, and as these hairs, you know, these hairs start washing around in this wave motion that's been set up by the sound, they change the potential, the electrical potential of the cell, and that, in turn, allows an electrical signal to be sent along the nerves into the brain.

Mr. FUCHS: Yeah, simple, isn't it?

PALCA: Yeah, yeah. Oh, I left out the glutamate. That's the chemical transmitter that…

Mr. FUCHS: That was excellent. You get a B+ for that.

PALCA: All right, yeah. Well, okay.

(Soundbite of laughter)

PALCA: So that's - but that's been known, right? I mean, this piece of neurophysiology or sensory physiology has been in textbooks for hundreds, if not - well, many hundreds of years.

Mr. FUCHS: That's right, so and the basic electrophysiology, the measurements and the recordings which have established that pathway, really started in the 1940s. The first reports of recordings from these nerve fibers, which carry information to the brain, were published by Galambos and Davis.

PALCA: Right.

Mr. FUCHS: So now, the thing is is that that's the kind of main pathway, and 95 percent of what happens, happens exactly like that, where there's one population of afferent neurons, these nerve cells that carry information to the brain, 95 percent of them are these large-diameter, so-called type one afferent neurons. And they report the brain everything that we know about sound -timing, intensity and frequency content. And that's what we've been able to learn about because they make up most of the nerve. And the studies were always done by taking a fine microelectrode to collect signals from individual nerve fibers and ask how they respond to sound.

So that's been the main story. The last remaining bit, though, was that there's a few neurons, those remaining five percent, which are much smaller. They have a different kind of arborization or innervation pattern in the cochlea, and we just couldn't find them. This process of sticking an electrode into the nerve, you just never found these little guys, so…

PALCA: So you can see them under the microscope, but you can't poke them with a recorder.

Mr. FUCHS: That's right. You could visualize them in various sorts of histological methods, and you knew they were there. In fact, from the turn of the 20th century, from the 19th to the 20th century, people first began to say look, there's these other interesting neurons there that had this very different arborization pattern, different branching pattern. What do they do?

PALCA: Ah, don't tell us yet. Don't tell us yet.

Mr. FUCHS: I won't.

PALCA: This is the cliffhanger.

Mr. FUCHS: Yeah.

PALCA: We have to stop for a second and take a break. So we have to find out what these type two neurons do. That's going to be interesting, and that's what we learn when come back after this short break. So stay with us.

(Soundbite of music)

PALCA: From NPR News, this is SCIENCE FRIDAY. I'm Joe Palca. We're talking this hour about sounds and how the brain hears them and some new, or some not so new but long known about nerve cells that now we think we know what they do.

We're talking with Paul Fuchs. He's the co-director of the Center for Sensory Biology at Johns Hopkins University in Baltimore, and we're taking your calls. The number is 800-989-8255, and when we left our hero, Paul Fuchs, we were just about to hear what these five percent of neurons which were too small to see in the past - now we've found a way to visualize them or listen to them or record from them and find out what the heck they're doing.

Mr. FUCHS: Right, and you know, the situation was so frustrating for a long time that people - some people even suggested that these weren't afferent neurons. Maybe they didn't signal to the brain at all. Maybe they just had something to do with activity within the cochlea itself.

But once the student who did this project, Catherine Weiss(ph), who goes by Cat(ph), began to work on this, she was able to develop a way to record from these very rare and mysterious type two neurons and determine that they, in fact, are afferents, that is that they are excited by glutamate release from hair cells just like the predominate type one neurons, and they're excitable. They generate the electrical signals that can propagate to the brain. So they definitely are afferent neurons.

PALCA: So they're going toward the brain.

Mr. FUCHS: Yeah.

PALCA: But it's interesting. It's an interesting idea that the brain is not only receiving signals from the ear, you think of that as a sort of an input device, but the brain is sending instructions to the ear, as well.

Mr. FUCHS: Yes, that's correct. So that's something else that we work on in our group, and we are trying to understand what those feedback signals from the brain are all about. In fact, nicely, these two things tie together because these type two afferent neurons that Cat has recorded from are contacting the hair cells, which are the target of this feedback pathway from the brain.

So it's almost like there might be a kind of a loop here, where the type two neurons may be specialized in some way to report on what these hair cells are doing that at the same time are being controlled by the brain.

PALCA: Okay, well, I think this is a good time to open the phones up to some of our listeners, and so let's take a call now. Let's first go to Bill(ph), in - is it Neda, Wisconsin? Bill in Neda, Wisconsin, welcome to SCIENCE FRIDAY. You're on the air.

BILL (Caller): Neda.

PALCA: Neda, okay. Well…

BILL: Could the expert comment on tinnitus, its process and possible treatment? I'll listen on the air.

PALCA: Okay, thanks. You mean tinnitus, I think.

BILL: Tinnitus, noise in the ear.

PALCA: Right, okay.

Mr. FUCHS: It depends on which side of the Atlantic you're on if it's tinnitus or tinnitus, to bring up on the country. But in any event, yeah, that's a really major issue of interest and clinical concern. Many people suffer from tinnitus. It can be profoundly disturbing in some cases. It's often associated with some degree of hearing loss.

Now, whether the present work helps us learn something about it is an interesting possibility. One of the ideas that people have floated is that tinnitus arises because there's been an imbalance in the kind of information coming to the brain because of some hearing loss in the periphery. And so maybe it has to do with the relative contributions of, say, type one and type two afferent neurons, which is why in part we're so excited about being able to work on these type two neurons. Specifically, because now, what we can do is define some molecular characteristics of those neurons and then be in the position to begin to think about how we might selectively alter their activity to test these kinds of ideas.

PALCA: I suppose we should close the loop here a little bit. We talked at the opening of the show about these - helping to explain how painful sounds are recognized, and we haven't really said how that works.

Mr. FUCHS: That's correct. So that was another one of the really, I think, exciting findings that Cat made, which is that these afferent neurons that she recorded from, these rare ones, are surprisingly insensitive. So if one delivers an equivalent kind of stimulus to the inner ear, the major type one neurons are very, very sensitive and respond very actively, but the type two neurons get only very weak input. So that if we translate this into thinking about sound, it suggests that these type two neurons would have to be exposed to very loud sound to be activated and send a signal to the brain.

So it might be that the two classes of neurons really divide up the auditory world into normal sound for the type one neurons and then very loud sound for the type two neurons. And that very loud sound is what, in some cases, is objectionable or painful to some people.

PALCA: Interesting. Okay, let's take another call now and go to Tony(ph) in Golden, Colorado. Tony, you're on the air for SCIENCE FRIDAY.

TONY (Caller): Hi, thanks for taking my call.

PALCA: Sure.

TONY: I'm a medical student, and we just took anatomy, and we postponed studying the vestibulocochlear nerve, the nerve for hearing. But I was curious about what nerve innervates those pain fibers, and could you also talk about the tensor tympani muscle controlling loud sounds?

PALCA: Ooh, that's another one I pronounce differently. I always called it the tensor tympani. How about that?

(Soundbite of laughter)

PALCA: Thanks, Tony, for the call.

TONY: Thank you.

Mr. FUCHS: Great, yeah. So these type two afferent neurons are in the same nerve, the eighth nerve, as the type one afferent neurons. So it's the same nerve route. So anatomically, in fact, they project to most of the same places in the central nervous system. So in that sense, they're anatomically in parallel.

Then you also ask about the tensor tympani. This is part of the acoustic reflex. This is actually innervated by motor neurons, which are activated by loud sounds. So one of our protective mechanisms is to clamp down the tensor, the eardrum a little bit by the tensor tympani that reduces its motion and so cuts down on the energy being transmitted into the inner ear, as does another muscles called the stapedius muscle, which connects up to one of the middle-ear ossicles and restricts its range of motion when it's contracting. So we have a lot of ways in which we can protect the ear from damage, and that's one of them.

PALCA: If we're going to talk about the tensor tympani, we'd be long to leave out the stapedius, don't you think?

(Soundbite of laughter)

Mr. FUCHS: That's right, yes. I also like to talk about the stapedius.

PALCA: Right. We talk about them together. All right. That's the other small muscle in the middle ear. Let's take another call now and go to Jason(ph) in Cambridge, Massachusetts. Jason, you're on the air at SCIENCE FRIDAY.

JASON (Caller): Hey, thanks. I have a question regarding - actually two - a question and a comment.

PALCA: Okay.

JASON: First, the question is regarding - you mentioned that glutamate specifically is an important neurotransmitter from all the ear mechanisms to the brain. My question is whether glutamate as a dietary supplement can be helpful in any aspect of helping hearing.

My comment is regarding tinnitus, that I found since I had had trouble with that as a musician, that it seems my ears are sensitive not only to volume but to clarity of the signal. For example, digitally recorded or remastered music, I have less trouble with that than older, analog sources or home recordings that have more noise. So that's an observation, but if you could address my question, I'd be really happy.

PALCA: Jason, thanks very much for that.

Mr. FUCHS: Can I address the observation, too?

PALCA: Yeah, sure, go ahead.

JASON: Oh sure. Thanks.

Mr. FUCHS: No, that's an interesting point about the fact that you find different, you know, sort of more complex and more noisy sound more difficult to deal with, and that's a very common feature of some - whenever there's some hearing loss. And so as I mentioned, tinnitus often occurs in conjunction with some degree of hearing loss. And one of the consequences is it's much more difficult to sort out signals from noise, and so that would be consistent with your observation.

And then with respect to the question about the dietary glutamate, probably no connection whatsoever. I think it's very doubtful that dietary glutamate is going to be involved in regulating the degree to which any nerve cell, but in particular the ear, would use it as a neurochemical.

PALCA: You know, I think this question of pain in the ear is an interesting one, sensing pain. I know sometimes when I dump the recycling into the can in the garage, it's a very loud sound, and it really makes me wince. What is the pain coming from? Where - is it the pain that my hair fibers are saying ah, you know, stop, it's like being in a tsunami here, or is it something else?

Mr. FUCHS: Well, I think this is one of the great, unanswered mysteries. And one of the reasons we actually started this project was because we have colleagues here in the Center for Sensory Biology who study pain explicitly, though in the skin, the somatosensory part of pain, and they made some observations that kind of inspired us to look into the ear to ask if there were some parallels.

Now, I can't say that we've actually proven that to be the case yet, but it's certainly intriguing that these type two afferents that Cat has now recorded from not only serve as detectors of loud sound, but they're also sensitive to a chemical called ATP, adenosine triphosphate, which is itself a mediator of painful stimulation in the skin. So maybe, you know, maybe we're on the road here to being able to say something about why it is that loud sounds can be painful.

PALCA: That's very interesting. Let's take another call now and go to John(ph) in San Antonio, Texas. John, you're on the air.

JOHN (Caller): Yes, thank you.

PALCA: Sure.

JOHN: Yeah, I'm very sensitive to certain sounds, particularly concerts. I had an - I went to a concert with a friend and I was not able to stay because of the noise that just - I felt panicky. I felt like I wanted to run to the door, just escape. So probably other people have the same problem, I don't know, but there were certainly a lot of - you know, a lot, a lot of noise. The building that appeared to be vibrating to me. And I did - would then have to leave.


JOHN: Uh-huh. Thank you.

PALCA: Yeah. Sure. That's an interesting question. Are people - is there a difference in sensitivity to loud noises?

Dr. FUCHS: Absolutely. Yup. I mean, the clinical condition is referred to as hyperacusis. That is ultra sensitive hearing. And as that gentleman just described, in some instances, it can be debilitating. So he wasn't able to stay for the concert, had to go away from what would have - perhaps otherwise had been enjoyable experience. And for some people, it can be really acute, walking down the city street can be quite difficult to do. And so, again, this is clearly some pathological condition of the ear. But there must also, as well, be underlying genetic differences amongst people which confer, you know, greater sensitivity to - in hearing or greater possibilities of pathologies that then lead to the condition of hyperacusis.

PALCA: Let's take one more call from Mary(ph), this time in Pleasanton, California. Mary, welcome to SCIENCE FRIDAY. You're on the air.

MARY (Caller): Hi. Thank you. My questions has to do with ear damage caused by chemotherapy, specifically (unintelligible) for which I have a hearing loss as a result of it. There are certain sounds I simply cannot hear and other sounds I hear perfectly. And it affects my ability to enjoy a movie or to enjoy a conversation. And I'm just wondering if there's anything on the horizon that can deal with that problem. Through traditional hearing aids, hearing would not be very pleasant because they would amplify the sounds I already hear quite well.

PALCA: Right. Okay. You know the answer.

Dr. FUCHS: Yes. Thanks, Mary. So you pointed out one of the causes of the hearing loss in our populations is due to chemotherapies. And other is that some of forms of antibiotics are also ototoxic. They poison the ear, and what they're poisoning are the sensory hair cells. These are very energetically active and demanding cells which are easily damaged. And so, some kinds of drugs do that.

And once damaged, then - if they're damaged severely enough, they die off. And, unfortunately, our sensory hair cells don't regrow - our being mammals - so we don't have the capacity to regenerate these hair cells. And so we'd lost that region of the cochlea's sensitivity forever. Now, that typically tends to be the higher frequencies because those hair cells are more sensitive.

PALCA: Mm-hmm.

MARY: Exactly. I don't hear little children well, and I have to stop my teaching career.

Dr. FUCHS: Well, then there are tuneable hearing aids. I mean, they are now at the point where hearing aids can be adjusted to the particular form of hearing loss that the individual has. Of course, you're talking about a more expensive instrument, but there are continuing advances in the prosthetics here, the ability to design a hearing aid which has specific kinds of amplification for specific kinds of hearing loss.

PALCA: Mary, thanks so much for bringing that up. And thank - it's an interesting point about hearing loss. I've had experienced it in my own family. We're talking to Dr. Paul Fuchs. He's the codirector of the Center for Sensory Biology at Johns Hopkins. And we're taking your calls at 800-989-8255.

I'm Joe Palca and this is SCIENCE FRIDAY from NPR News.

We also have a question from "Second Life" which - it was occurring to me, the question is from P.R. Mantis(ph). And it goes, how close are we to stem cell or other gene therapy for high-end hearing loss to the hair cell damage?

Dr. FUCHS: That's a very, very important issue. It's something that many laboratories are working on with a great deal of vigor and effort. It's a particularly challenging problem for the ear because the anatomy of the ear is so complex and so elegant. And one of the things that has stymied people is that the inner ear of the - of we, mammals, doesn't regenerate hair cells after damaged, whereas other kinds of tissues do. And the inner ears of other vertebrates do, so birds and reptiles and amphibia can grow their hair cells perfectly happily after damage.

So the question is what's going on in the inner ear? Why does it not regenerate itself? Are there no stem cells there? Or if we put stem cells in, will they just simply fail to propagate? And even if they did propagate, will they build the right structure?

So the whole functioning of the ear is essentially dependent upon this very elegant mechanical tune-vibrating membrane that lies within the cochlea. And to reconstruct, as you might imagine, will be quite a difficult task. Nonetheless, it's being attempted, and people are working on ways to try to get stem cells to grow in the ear. There's also efforts being made to cause the - re-surviving nerve cells even after the sensory hair cells are gone. If you can encourage the growth of the surviving nerve cells, then the cochlear implant, for instance, could work much better. So there are several different strategies being pursued.

PALCA: Well, it sounds like a really interesting time for otolaryngology and auditory research.

Dr. FUCHS: It absolutely is.

PALCA: Okay. Paul Fuchs, thank you so much for joining us.

Dr. FUCHS: My pleasure, Joe.

PALCA: Paul Fuchs is codirector of the Center for Sensory Biology at Johns Hopkins University in Baltimore. He's also the John Bordley professor and director of otolaryngology at research there. Thank you very much.

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