A single bundle of stereocilia (green) projects from the epithelium of the papilla, a sensory patch in amphibian ears. We can enjoy music and hear the city traffic because of stereocilia bundles in the inner ear. These actin-rich bundles protrude from the apical surface of hair cells lining the inner ear and vibrate in response to sound waves.

By Leonardo Andrade and Bechara Kachar, NIDCD/NIH

Researchers Discover Two-Step Mechanism of Inner Ear Tip Link Regrowth: Mechanism Offers Potential for Interventions That Could Save Hearing

A team of NIH-supported researchers is the first to show, in mice, an unexpected two-step process that happens during the growth and regeneration of inner ear tip links. Tip links are extracellular tethers that link stereocilia, the tiny sensory projections on inner ear hair cells that convert sound into electrical signals, and play a key role in hearing. The discovery offers a possible mechanism for potential interventions that could preserve hearing in people whose hearing loss is caused by genetic disorders related to tip link dysfunction. The work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD), a component of the National Institutes of Health.

The findings appear in the June 11, 2013 online edition of PLoS
Biology. The senior author of this study is Gregory I. Frolenkov, an associate professor in the College of Medicine at the University of Kentucky, Lexington, and his fellow, Artur A. Indzhykulian, Ph.D., is the lead author.

Stereocilia are bundles of bristly projections that extend from the tops of sensory cells, called hair cells, in the inner ear. Each stereocilia bundle is arranged in three neat rows that rise from lowest to highest like stair steps. Tip links are tiny thread-like strands that link the tip of a shorter stereocilium to the side of the taller one behind it. When sound vibrations enter the inner ear, the stereocilia, connected by the tip links, all lean to the same side and open special channels, called mechanotransduction channels. These pore-like openings allow potassium and calcium ions to enter the hair cell and kick off an electrical signal that eventually travels to the brain, where it is interpreted as sound. 

The findings build on a number of recent discoveries in laboratories at the NIDCD and elsewhere that have carefully plotted the structure and function of tip links and the proteins that comprise them. Earlier studies had shown that tip links are made up of two proteins—cadherin-23 (CDH23) and protocadherin-15 (PCDH15)—that join to make the link, with PCDH15 at the bottom of the tip link at the site of the mechanotransduction channel, and CDH23 on the upper end. Scientists assumed that the assembly was static and stable once the two proteins bonded.

Tip links break easily with exposure to noise. But unlike hair cells, which can’t regenerate in humans, tip links repair themselves, mostly within a matter of hours. The breaking of tip links, and their regeneration, has been known for many years, and is seen as one of the causes of the temporary hearing loss you might experience after a loud blast of sound (or a loud concert). Once the tip links regenerate, hair cell function returns, usually to normal levels. What scientists didn’t know was how the tip link reassembled.

To study tip link assembly, the researchers treated young, postnatal (5-7 days) mouse sensory hair cells with BAPTA—a substance that, like loud noise, damages and disrupts tip links. To image the proteins, the group pioneered an improved scanning electron microscopy (SEM) technique of immunogold labeling that uses antibodies bound to gold particles that attach to the proteins. Then, using SEM, they imaged the cells at high resolution to determine the positions of the proteins before, during, and after BAPTA treatment.

What the researchers found was that after a tip link is chemically disrupted, a new tip link forms, but instead of the normal combination of CDH23 and PCDH15, the link is made up of PCDH15 proteins at both ends. Over the next 24 hours, the PCDH15 protein at the upper end is replaced by CDH23 and the tip link is back to normal.

Why tip links regenerate using a two-step instead of a neat one-step process is not known. For reasons that are still unclear, CDH23 disappears from stereocilia after noise damage while PDCH15 stays around.  Looking to regenerate quickly, the lower PDCH15 latches onto another PDCH15, forming a shorter and functionally slightly weaker tip link. Later, at some time during the 36 hours after the damage, when CDH23 returns, PDCH15 gives up its provisional partner and latches onto its much stronger mate in CDH23. In other words, PDCH15 prefers to be with CDH23, but in a pinch it will bond weakly with another bit of PDCH15 until CDH23 shows up.

The researchers coupled the SEM observations with electrophysiology studies to show how the functional properties of the tip links changed throughout this two-step process. The temporary PCDH15/PCDH15 tip link has a slightly different functional response than the permanent PDCH15/CDH23 combination. Researchers were able to correlate the differences in function with the protein combinations that make up the tip link.

Additional experiments revealed that when hair cells develop, the tip links use the same two-step process.

Previous research has shown that both CDH23 and PCDH15 are required for normal hearing and vision. In fact, NIDCD scientists in earlier studies have shown that mutations in either of these genes can cause the hearing loss or deaf-blindness found in Usher Syndrome types 1D and 1F. 

“In the case of deaf individuals who are unable to make functional CDH23, knowledge of this new temporary alliance of PCDH15 proteins to form a weaker, but still functional, tip link could inform treatments that would encourage the double PCDH15 bond to become permanent and maintain at least limited hearing,” said Tom Friedman, Ph.D., chief of the Laboratory of Molecular Genetics at the NIDCD, where the research began.

31 July 2013

New Ear-a

Inside our ears lies a very sophisticated system, responsible not only for our hearing but also for detecting motion and keeping our balance. To do this, the cells of the inner ear use sensory hairs, or stereocilia, which bend in response to vibrations, triggering a cascade of events to send a signal to the brain. Researchers have recently managed to generate these sensory cells from mouse embryonic stem cells, by treating them with a series of molecules known to be necessary for their development. The finished cells, pictured in red, with their nuclei in blue and bundles of stereocilia in green, have all the characteristics of cells found in the vestibular apparatus, the region of the inner ear involved in perceiving movement. Growing these cells in the laboratory will help further our understanding of inner ear development, as well as test potential treatments of diseases affecting hearing and balance.

Written by Emmanuelle Briolat

Dr. Sonja Pyott
University of North Carolina, Wilmington
Specimen: Cochlea and Hair Cells
Technique: Confocal

Mammalian organ of Corti - the epithelium which contains the sensory hair cells of the ear (stained green here). The inner hair cells are in the lower left, and the three rows of outer hair cells are to the upper right. Nuclei of the inner hair cells are blue and the spindly red things are the neurons, which are synapsing on the inner hair cells’ surface. The spiky things shooting out of the top of the inner hair cells are the stereocilia (which are made of actin, so green) which project into the fluid filled space above the organ of Corti. When sound waves are picked up by the ear canal and focused into the cochlea, the basilar membrane vibrates, causing the stereocilia to bend, which depolarizes the hair cells.


New findings on the workings of the inner ear

The sensory cells of the inner ear have tiny hairs called stereocilia that play a critical part in hearing. It has long been known that these stereocilia move sideways back and forth in a wave-like motion when stimulated by a sound wave. After having designed a microscope to observe these movements, a research team at Karolinska Institutet has discovered that the hairs not only move sideways but also change in length.

The discovery, which was made in collaboration with scientists at Baylor College of Medicine in Texas, USA provides new fundamental knowledge about the mechanisms of hearing. It is presented in the online scientific journal Nature Communications.

30 September 2013

I Hear You

Deep inside our ears is a bristling forest of tiny fingers. These are stereocilia – microscopic hair-like structures that wobble in response to sound waves. Their movement triggers signals to the brain that get interpreted as noises from the world around us, from The Beatles to breaking glass. Problems with the stereocilia can cause deafness, so scientists are trying to understand the molecules that make them in order to find cures. These red fronds are the developing stereocilia in a baby rat’s ear, stained with a fluorescent dye, while the green dots reveal the locations of two different molecules. The one highlighted in the image on the left helps to build the delicate structures early on, while the one on the right helps to maintain them throughout life. Figuring out how these molecules work – or don’t work in deaf people – could provide future solutions for hearing loss.

Written by Kat Arney

Although 12 years old Spirit of Gravity is still getting the punters in, and there is a tangible feeling of excitement tonight.  Ostensibly avant-garde music promoters, they remain fresh within that oft-humourless medium, by mixing the serious, the ridiculous and the ridiculously good.  Like tonight.

Stereocilia is London-based sound-artist John Scott.  His set is composed of layers of soft harmonics and interweaving chords that harbour post-rock, then some tasty 70s space-rock.  At one stage the drones and chiming guitars can’t help but evoke an Indian flavour.  Just as the audience are completely hypnotised into submission, he is gone.  Mission accomplished.

One of the highlights from any Spirit of Gravity event is the Electrocrèche.  A selection of ever-revolving charity shop keyboards set up for the audience to abuse between acts.  You can either create the most beautiful cacophony of your life, or take masochistic delight in knowing that repeatedly hitting the highest key over and over is being broadcast round the building.  Playing the Electrocrèche does highlight how much effort SoG put in.  Suits you sir!

There comes a point in everyone’s life where you want to watch two fully frown men jump up and down making astonishingly agonised bird impressions through contact-mics in front of a radiating goose lamp. That somehow, is exactly what DOGEESESEEGOD do.  Interestingly, from the vantage point of that odd corner-space in Green Door Store the room started to smell of dog food.  Was this intentional?  The show starts off very funny, but after ten minutes it becomes painfully clear that only the bands mates are still laughing, after 15 minutes they mercifully stop.

After all that bluster comes the more measured disorder of ARC.  What really sets the local improv mainstays apart from many of their contemporaries – asides from their sheer breadth of skill – is the subtle use of electronics.  There was a real feeling of community while they were playing, as every abstract effect produced a ‘what was that?’ reaction in the audience, provoking a shared sense of puzzlement.  Which when you consider the trio of violin, double-bass and cello are have been making music since the 80s it’s impressive they aren’t taking a safer approach.  They perplexing end with a country hoe-down?

That’s the good thing about Spirit of Gravity.  You are always kept guessing.

01 March 2014

Hearing and Headbobbing

More than 800,000 people in the UK – including 45,000 children – are deaf. To understand more about what’s going on when people lose their hearing or are born deaf, researchers are studying mice with a genetic fault called headbobber. Animals with the faulty gene have distinctive ear problems, including deafness, poor balance and, as the name suggests, characteristic head-bobbing. Looking more closely, the delicate hairs inside the ear - known as stereocilia – don’t form properly in headbobber mice (bottom row of images), compared to normal animals (top row). The exact gene responsible still needs to be identified, but it’s likely to be important for the growth and organisation of the inner ear – the part responsible for hearing and balance. Headbobber mirrors a genetic fault in humans with similar hearing and balance problems, so the researchers hope their bobbing mice will shed light on the condition in humans.

Written by Kat Arney

Image courtesy of Karen Steel and colleagues
Wellcome Trust Sanger Institute, UK
Originally published under a Creative Commons Licence (BY 4.0)
Research published in PLOS One, February 2013

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I really miss Melbourne and fucking hate the suburbs.

I kinda hate sleeping in the suburbs now. There’s no cars driving past, no trams rattling down the street, no bands across the road, and nothing to drown out the ringing in my ear. My left ears getting worse. I think it’s because I stand on the left of gigs, although it’s definitely because I’ve flattened my stereocilia one too many times. See the stereocilia are the tiny little hairs inside the ear, and mine happen to snapping after being flattened too many times. When you’re younger they’re able to push themselves back up and stand straight and bend back and forth at 18000 19000 times a second But as you get older and they get flattened too many times they eventually snap and die. The continuous ringing you hear is the last little gasp of a dying stereocilia. It won’t ever be replaced and your hearing slowly becomes less and less sensitive. So when I sleep in the suburbs there’s nothing to drown out that little stereocilia that just won’t let go.