Brain scientists at Johns Hopkins have discovered how
cells in the developing ear make their
own noise, long before the ear is able to detect sound
around the cells. The finding, reported Nov. 1 in
Nature, helps to explain how the developing auditory
system generates brain activity in the absence of
sound. It also may explain why people sometimes experience
tinnitus and hear sounds that seem to
come from nowhere.
The research team made its discovery while studying
the properties of non-nerve cells in the
ears of young rats. These so-called support cells were
thought to be silent bystanders not directly
involved in nerve communication. However, to the
researchers' surprise, these cells showed robust
electrical activity, similar to the way nerve cells do.
Further, this activity occurred spontaneously,
without sound or any external stimulus.
"It's long been thought that nerve cells that connect
auditory organs to the brain need to
experience sound or other nerve activity to find their way
to the part of the brain responsible for
processing sound," said the study's lead author, Dwight
Bergles, an associate professor of
neuroscience at Johns Hopkins. "So when we saw that
these supporting cells could generate their own
electrical activity, we suspected they might somehow be
involved in triggering the activity required
for proper nerve wiring."
Bergles' team suspected that a chemical might be
involved in these cells' generating electrical
pulses, so they applied a number of different candidate
drugs and chemicals to the developing
cochlea — the small hollow and liquid-filled chamber
in the inner ear that converts sound waves to
electrical signals — hoping to block the mystery
trigger. The few drugs that altered the electrical
output all disabled ATP (adenosine triphosphate), a
chemical used most often as a cell's energy
currency but also, as in this case, as a signal to
communicate with other cells.
According to Bergles, a breakthrough came when it was
discovered that ATP also caused the
supporting cells to change their shape. By simply
videotaping the developing cochlea, the team was able
to monitor where and when ATP was released. After studying
these movies, they found that ATP was
being released near hair cells, which are responsible for
transferring sound information to auditory
nerves. It was known that hair cells have receptors for
ATP, so the researchers thought they might
also be affected by the ATP released from the supporting
cells. Indeed, the team found that hair
cells also showed spontaneous electrical activity, which
occurred at the same time as the responses in
neighboring support cells and was blocked by drugs that
block ATP receptors.
In a dominolike effect, ATP then signals the hair
cells to release another chemical, glutamate,
which then activates the nerve cells that project into the
brain. "It is as if ATP substitutes for sound
when the ear is still immature and physically incapable of
detecting sound," said Bergles, adding that
"the cells we have been studying seem to be warming up the
machinery that will later be used to
transmit sound signals to the brain.
"We think that only a few cells release ATP at one
time," he said. "And that small amount of
free-floating ATP then activates only a few nearby hair
cells." This may help associated nerve cells,
far away in the depths of the brain, figure out who and
where their neighbors are.
Bergles acknowledges that his experiments beg the
question of why a human or any animal would
need to "hear" before birth. He speculates that the ability
to hear subtle differences, like the
inflection in one's voice, "requires a lot of fine-tuning
based on where in the brain the nerves connect.
It could be that brief bursts of electrical activity in
just a few nerve cells at a time help do that fine-
tuning so the system works well."
While this activity likely is essential for the
auditory system's proper development, it could be
bad in the adult, mature nervous system, Bergles said, as
it would trigger electrical signals in the
absence of sound. However, as the ear matures during the
first two weeks of a rat's life, most of the
cells that release ATP disappear, so by the time the rat
can hear sound, all the spontaneous electrical
activity in its ears has stopped.
Although there is no ATP floating around at that
point, the hair cells continue to be able to
respond to it, and exposure to loud sounds can trigger ATP
release in the ear. Bergles said he suspects
that "if ATP were released by the remaining support cells,
it may cause the sensation of sound when
there is none," a condition known as tinnitus, or ringing
in the ears. Alternatively, he noted that bursts
of activity might trigger changes in the connectivity of
neurons in the brain, just as it does during
development, eventually leading to abnormal activity that
is perceived as sound.
The research was funded by the National Institutes of
Health.
Authors on the paper are Nicolas Tritsch, Eunyoung Yi,
Elisabeth Glowatzki and Bergles, all of
Johns Hopkins; and Jonathan Gale, of University College
London.
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