Unraveling the Mysteries of the Inner Ear
When researcher Paul Fuchs talks about the cochlea, you can almost hear him sigh. “Once I began working in the inner ear, and saw how extraordinarily beautiful it is, the detail, the anatomy, the differentiation on a functional level, the biophysics… it’s this amazingly sophisticated, elegant biological mechanism, and I decided that was where I was going to work.”
That passion has helped Fuchs uncover the neurochemistry of hearing, the actual molecules that carry electrical signals from the cochlea’s hair cells to the brain for processing. While some deafness and hearing loss can be treated with mechanical aids such as cochlear implants, Fuchs’ work might someday yield drug or gene therapies that get at the root causes of hearing deficits.
Because the cochlear is so difficult to work with—its tissues and cells are encased in the body’s hardest bone, existing in separate compartments each with its own special fluid balance and gradients—it’s been harder to define the biochemical mechanisms of hearing than those for other senses such as sight or smell. Fuchs and fellow researcher Elisabeth Glowatzki have spent years mapping these pathways.
Glowatzki looks at glutamate, the chemical released when a hair cell sends its electrical signal upstream. Her previous work found that the cells package glutamate in tiny vesicles that cluster together at micron-size ribbons similar to those used by photoreceptor cells in the eye. Like a raft full of passengers, the ribbons dock opposite a nearby auditory neuron that passes the glutamate signal along. Glowatzki recently proved that the connection is vital by showing that mice lacking the ability to release glutamate are profoundly deaf. She says her findings could have implications in humans. “If you can test for a gene that shows the absence of glutamate with a given deafness, we can say, Well, the nerve fibers are still intact, so a cochlear implant would help.”
Meanwhile, Fuchs is studying the brain’s feedback mechanism in the cochlea’s outer hair cells, which are designed to amplify incoming sound waves. Thus, the brain operates like a soundman at a concert, modulating the volume and frequencies amplified by those outer hair cells at the source so that what we hear isn’t a cacophony, but a symphony. Fuchs and his colleagues recently created mice with a single mutation that alters the chemistry at a nicotinic receptor between the brain and the hair cells. As a result, the brain exerts a stronger feedback effect that protects the mice against noise-induced hearing loss.
Fuchs says that while nicotinic receptors are common throughout the body, “the one in the ear is genetically and pharmacologically distinct from others. So, it should be possible to find chemicals that act specifically in the ear and not in the brain or muscles that have other nicotinic receptors. That’s great because we could discover ear-specific drugs to take on noise-induced hearing loss.”