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So the researchers explored what would happen when they created “knockout” mice that had no alpha-10 subunit. They reported their findings in the December 18, 2007, Proceedings of the National Academy of Sciences.
Their first measurements of the physiological functioning of the basic machinery of the animals' auditory system indicated that it functioned perfectly well. Then they conducted more subtle physiological tests that specifically measured whether the animals' efferent auditory systems were working properly. To determine how the ears of the mice responded to different sound frequencies, the researchers inserted electrodes into the auditory nerves of the mice and placed delicate microphones next to the outer hair cells. Those tests revealed that, although the animals' basic hearing was intact, the efferent systems in the mice lacking the alpha-10 subunit were not fully functional at the electrophysiological level. The outer hair cells in those mice did not respond normally to bursts of acetylcholine from efferent neurons.
Establishing the physiological role of the alpha-10 subunit represents only the beginning of their explorations into its function, says Elgoyhen. Her lab has already started cloning the chicken versions of the alpha-10 and alpha-9 subunits.
“We are comparing the properties of the chicken receptor to the mammalian receptor,” she says, “to see if there is some functional difference between them that can tell us why this alpha-10 subunit uniquely evolved a special role in mammals compared with nonmammalian vertebrates.” What's more, Elgoyhen and her colleagues plan to explore the more subtle hearing consequences of loss of the alpha-10 subunit and thus a fully functional efferent system.
“So far, we only know that without the subunit, the efferent system does not work,” she says. “Now, we are investigating the consequences at the level of behavior—whether the knockout mice show a difference in protection from sound injury or in attentional behavior.”