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January 2009--Of the five senses, hearing seems to be the one most often linked to daily nuisances. After all, whether it’s a chatty neighbor on the airplane, your unruly upstairs renters, or even a cubicle mate typing just a bit too emphatically, it’s sound that typically bothers us the most.
But while that’s the case, hearing should also get its due as one of our most fascinating, and efficient, areas of perception. As Angelika Doetzlhofer—who in November joined Neuroscience and the Center for Sensory Biology (CSB) as one of Hopkins’ newest faculty members— notes, “a mouse, for example, has millions of photoreceptors in each eye to take in light, but only about 3,000 hair cells in each ear to process sound.”
It’s 3,300, to be a little more precise (though humans have around 15,000 per ear at birth), arranged within the cochlea in four orderly rows of inner and outer hair cells and tasked with converting sound waves in electrical information to be sent to the brain. And here at Hopkins, Doetzlhofer joins a strong group of researchers figuring out how our auditory system does so much with so little.
Doetzlhofer is most keenly interested in the development of hair cells and their death. Losing even one hair cell can adversely affect hearing, and as the cells die from injury or infection or even plain aging, they do not grow back…in mammals, at least.
“We know that in birds, supporting cells similar to the glial cells in the brain can re-enter the cell cycle and give rise to new hair cells when one dies,” she says. So why are mammalian hair cells lacking? Is it due to an intrinsic inability of supporting cells to differentiate or just a forced blockade of regenerative signals? That was the basis of Doetzlhofer’s postdoctoral studies at the House Institute for Hearing in Los Angeles.
Fortunately, it seems the inability to restore lost hair cells is not inherent. While at House, Doetzlhofer managed to coerce supporting cells purified from mouse cochleae to divide and produce new hair cells in culture. The loss of cell proliferation potential arises in part, it seems, from changes in the ability to inhibit a protein called p27(Kip1) that regulates the cell cycle. With this uplifting preliminary work in tow, Doetzlhofer begins her Hopkins career trying to figure out how to duplicate these results in living mice.
CSB co-director Paul Fuchs is one of many eager to see how those mouse studies turn out. “There have been great strides in treating auditory disorders with surgery or electrodes,” he says, “but neuropharmacology for the ear is severely lacking. Think about all the drugs we have to modulate neurons in the brain. We don’t have a single drug that works selectively on neural signaling in the ear.”
We’re still many years and manhours away, however, before we reach the day where a few ear drops might restore dead hair cells or treat other auditory disorders like tinnitus (continual buzzing) or hyperacusis (overly- sensitive hearing). On his end, Fuchs, who is also a professor of otolaryngology– head and neck surgery, biomedical engineering and neuroscience, has been working toward that goal by focusing on how hair cells and the brain communicate.
“Hair cells release neurotransmitters through special structures known as ribbon synapses,” he says, “which differ from conventional synapses in that they release their chemicals rapidly and continuously, explaining in part why our ears are always on.” In 2002, Fuchs and otolaryngology– head and neck surgery colleague Elisabeth Glowatzki described the mechanism behind ribbon synapse function in hair cells (they simultaneously release multiple vesicles filled with the chemical glutamate), and he notes that since then, Glowatzki’s lab has been a leader in detailing this process much further.
Fuchs’ efforts also cover the other side of the synaptic equation, by examining the signals that hair cells receive. While the ribbon synapses don’t shut down, the sensory hair cells are subject to inhibitory feedback from the brain that can adjust how sensitive the ears are. These efferent neurons release the neurotransmitter acetylcholine, which binds to specialized ion channels that Fuchs’ lab characterized and helped identify.
“Interestingly, though there are some important differences, synaptic signaling by hair cells shows striking parallels with that of photoreceptors in the eye.” Fuchs adds, “This highlights why a center like the CSB can be so valuable: The senses are functionally distinct yet interrelated at the level of molecular mechanisms.”