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Seeing, Hearing and Smelling the World

It's All in the Brain
Breaking the Code of Color
How We See Things That Move
The Quivering Bundles That Let Us Hear
Signals From a Hair Cell
The Goal: Extreme Sensitivity and Speed
Tip Links Pull Up the Gates of Ion Channels
Locating a Mouse By Its Sound
The Mystery of Smell
A Secret Sense in the Human Nose?
New Imaging Techniques That Show the Brain at Work
Progress Continues
The Quivering Bundles That Let Us Hear:
The Goal: Extreme Sensitivity and Speed

Because of the hair cell bundles' uncanny resemblance to little antennae and their location in the inner ear, the cells had long been suspected of playing an important role in hearing. This view was bolstered by clinical evidence that the majority of hearing impairments—which affect some 30 million Americans—involve damage to hair cells.

There are only 16,000 hair cells in a human cochlea, compared to some 100 million photoreceptors in the retina of the eye, and they are extremely vulnerable. Life in a high-decibel society of pounding jackhammers, screeching subway cars, and heavy metal rock music can take a devastating toll on them. But whatever the cause—overexposure to loud noises, disease, heredity, or aging—people tend to lose 40 percent of their hair cells by the age of 65. And once destroyed, these cells do not regenerate.

"The mechanics of the hair cell are fascinating—the fact that simply pushing a little bundle of cilia magically allows us to hear. And the cells are beautiful. I never get tired of looking at them," says David Corey.

Corey and James Hudspeth, an HHMI investigator at the Rockefeller University, have explored the microscopic inner workings of hair cells in finer and finer detail over the past 20 years, gaining a solid understanding of how the cells work

Some pieces of the puzzle have fallen into place recently with the discovery of a unique mechanism that endows hair cells withe their two most distinctive properties—extreme sensitivity and extreme speed.

Protected deep inside the skull, hair cells cannot easily be studied in living creatures. Yet once they are removed from laboratory animals, these cells quickly die. Even now, Corey acknowledges, "a good experiment would be to study three or four cells for maybe 15 minutes each."

Though such experiments are now routine in their labs, they remain tricky. The measurements are so delicate that they are usually carried out on a table mounted on air-cushioned legs, to reduce any external movements or vibrations; otherwise, the building's own vibration would deafen a hair cell in seconds.

Hudspeth found that an unused swimming pool built on bedrock in a basement at the University of California, San Francisco, where he worked previously, made the perfect laboratory for hair cell experiments—especially after he had it filled with 30 truckloads of concrete for more stability.

Hair cells from bullfrogs were exposed by removing the sacculus, a part of the inner ear, and pinning the pinhead-sized tissue to a microscope slide. Working under a microscope, Hudspeth and Corey were then able to manipulate an individual hair cell's bundle of cilia with a thin glass tube.

They slipped the tube over the bundle's 50 to 60 stereocilia, which are arranged like a tepee on the top of each hair cell, and moved the tube back and forth, deflecting the bundle less than a ten thousandth of an inch. The hair cell's response was detected by a microelectrode inserted through the cell membrane.

Corey and Hudspeth found that the bundle of stereocilia operated like a light switch. When the bundle was prodded in one direction—from the shortest cilia to the tallest—it turned the cell on; when the bundle moved in the opposite direction, it turned the cell off.

Based on data from thousands of experiments in which they wiggled the bundle back and forth, the researchers calculated that hair cells are so sensitive that deflecting the tip of a bundle by the width of an atom is enough to make the cell respond. This infinitesimal movement, which might be caused by a very low, quiet sound at the threshold of hearing, is equivalent to displacing the top of the Eiffel Tower by only half an inch.

At the same time, the investigators reasoned that the hair cells' response had to be amazingly rapid. "In order to be able to process sounds at the highest frequency range of human hearing, hair cells must be able to turn current on and off 20,000 times per second. They are capable of even more astonishing speeds in bats and whales, which can distinguish sounds at frequencies as high as 200,000 cycles per second," says Hudspeth.

Photoreceptors in the eye are much slower, he points out. "The visual system is so slow that when you look at a movie at 24 frames per second, it seems continuous, without any flicker. Contrast 24 frames per second with 20,000 cycles per second. The auditory system is a thousand times faster."

— Jeff Goldberg

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When this bundle of 50 to 60 cilia at the top of a hair cell vibrates in response to sound, the hair cell (from a bullfrog's inner ear) produces an electrical signal. Tiny tip links can be seen joining the tops of shorter cilia to the sides of the taller ones.

Photo: John Assad, Gordon Shepherd and David Corey, Massachusetts General Hospital






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