Researchers Describe ‘Volume Control’ Pathway for Hearing

by Jim Schnabel

April 8, 2009

Researchers have genetically engineered mice whose hearing is much less vulnerable to damage from loud ambient noise. The new technique highlights a feedback system in the brain that protects ear cells and suggests how it might be altered.

“Developing a pill to mimic the effects of the mutation could certainly be one way to go,” says Stéphane Maison, a researcher at Harvard Medical School who was a co-author on the paper. In the nearer term, “by exploring the strength of this system in a population at risk, for instance factory workers exposed to loud sounds, one could screen individuals most at risk in noisy environments and take appropriate steps to protect those individuals even more.”

 The feedback system targeted by the international team of researchers is called the medial olivocochlear (MOC) pathway. It is made up of neurons in the midbrain whose output fibers reach into the cochlea, the spiraled sound-sensing organ in the inner ear.

When sound levels detected by the brain reach a certain threshold, MOC neurons become active and send signals to primary amplifier cells in the cochlea known as outer hair cells, turning down their activity and thus reducing the signal sent to the auditory cortex through the auditory nerve.

To find out more about how this MOC “volume control” pathway works, the researchers mutated lab mice, targeting a subunit of the receptor on hair cells that normally detects incoming MOC signals. They found that a particular “point mutation,” in which a single nucleotide is altered at a key location in the receptor gene, caused the receptor to become extra-sensitive to MOC feedback signals—moderately damping auditory perception in the mice and markedly prolonging the MOC response to a loud noise.

In a related set of experiments, the researchers exposed both normal mice and the mutant-receptor mice to excessive levels of sound and found from subsequent tests that the mutant mice showed much less evidence of hearing loss than the normal mice. Mice with one normal copy of the receptor gene and one mutant copy had an intermediate level of protection, underscoring the causal role of the mutant gene.

Earlier research showed that the MOC pathway could protect against hearing loss, but there is no consensus on whether it evolved to have that specific function. “We don’t know if it’s an epiphenomenon related to its main function or not,” says Maison. “Personally, I think that if it’s there, it must serve a purpose.”

John Guinan, a professor of otology and laryngology at Harvard Medical School who was not involved in the study, notes that the MOC pathway is also studied for its other presumed function in hearing: as a filter of unimportant or unwanted sounds.

There is good evidence, Guinan says, that MOC feedback nerves, or “efferents,” help to suppress background noises so that any new and perhaps interesting noise can be perceived more clearly. There is also some evidence “that attention turns on efferents,” he says. “For example, if there’s a noise in the background and you’re trying to read something or do a visual task, you can turn on your efferents and can sort of turn down the gain of the background noise a little bit”—possibly with a selectivity that enables unwanted sound frequencies to be suppressed.

Although this would be the most logical function for the MOC pathway, and would partly explain—for example—the “cocktail party effect,” in which humans are able to perceive another speaker clearly amid several talking at once, Guinan notes that it is difficult to study the pathway in humans. “We don’t really understand how good a job the efferents do, and under what circumstances they work. That still is an open research problem.”

The paper was published online Jan. 20, 2009, at the Public Library of Science (PLoS) Biology Web site.