BME Seminar Series: Jonathan Fisher, Ph.D.

Light and Sound: An optical approach for illuminating the elusive mechanics of hearing in the mammalian cochlea

Postdoctoral Fellow, Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University

Abstract

Human hearing is exquisitely sensitive over a vast range of sounds. We can hear faint sounds down to the level of thermal fluctuations in the ear, and our ability to discern subtle differences in tone allows us to distinguish human voices of nearly identical timbre. We additionally perceive sounds of vastly differing intensities on a similar scale, enabling us to clearly hear the distant strumming of nylon strings from a classical guitar playing in concert with a full orchestra. These remarkable capabilities are largely lost in individuals with sensorineural hearing loss, which affects millions of Americans. In many cases, the symptoms of such hearing loss are consistent with a loss of active hearing, a process by which hair cells of the inner ear nonlinearly amplify their own mechanical stimuli.

The biomechanical origin of this active process, however, remains elusive. Prestin, a unique motor protein, causes electrically evoked length changes in the cochlea's sensory hair cells. This effect is thought to be essential and even sufficient for cochlear amplification. Using a scanning heterodyne interferometer, we measured sound-evoked traveling waves in the mammalian cochlea in vivo. We combined these interferometric measurements with targeted, protein-specific photo-deactivation of prestin’s motor properties in selected cells. Using this optical manipulation, which utilized photolabile organic compounds, we observed how the ear's response to sound is shaped by prestin's electromotile forces.